Metabolic reprogramming and dysregulated metabolism: Cause, consequence and/or enabler of environmental carcinogenesis?

Carcinogenesis

Volumn 36, Issue , 2015, Pages S203-S231

  Brooks Robey, R ^a,b   Weisz, Judith ^c   Kuemmerle, Nancy ^a,b   Salzberg, Anna C ^c   Berg, Arthur ^c   Brown, Dustin G ^d   Kubik, Laura ^e   Palorini, Roberta ^f   Al Mulla, Fahd ^g   Al Temaimi, Rabeah ^g   Colacci, Annamaria ^h   Mondello, Chiara ⁱ   Raju, Jayadev ^j   Woodrick, Jordan ^k   Ivana Scovassi, A ⁱ   Singh, Neetu ^l   Vaccari, Monica ^h   Roy, Rabindra ^k   Forte, Stefano ^m   Memeo, Lorenzo ^m   Salem, Hosni K ⁿ   Amedei, Amedeo ^o   Hamid, Roslida A ^p   Williams, Graeme P ^q   Lowe, Leroy ^r,s   Meyer, Joel ^e   Martin, Francis L ^r   Bisson, William H ^t   Chiaradonna, Ferdinando ^f   Ryan, Elizabeth P ^d   more..

^a VA MEDICAL CENTER   (United States)

^b DARTMOUTH MEDICAL SCHOOL   (United States)

^c PENN STATE COLLEGE OF MEDICINE   (United States)

^d Food Science and Human Nutrition   (United States)

^e DUKE UNIVERSITY   (United States)

^f UNIVERSITY OF MILANO BICOCCA   (Italy)

^g KUWAIT UNIVERSITY   (Kuwait)

^h Center for Environmental Carcinogenesis and Risk Assessment   (Italy)

ⁱ CNR   (Italy)

^j TOXICOLOGY RESEARCH DIVISION   (Canada)

^k GEORGETOWN UNIVERSITY   (United States)

^l KING GEORGE'S MEDICAL UNIVERSITY   (India)

^m Mediterranean Institute of Oncology   (Italy)

ⁿ CAIRO UNIVERSITY   (Egypt)

^o UNIVERSITY OF FLORENCE   (Italy)

^p UNIVERSITY PUTRA MALAYSIA   (Malaysia)

^q UNIVERSITY OF READING   (United Kingdom)

^r LANCASTER UNIVERSITY   (United Kingdom)

^s Getting to Know Cancer   (Canada)

^t OREGON STATE UNIVERSITY   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ALDEHYDE DERIVATIVE; ENVIRONMENTAL CHEMICAL; METAL DERIVATIVE; ORGANOPHOSPHATE; PYRETHROID; CARCINOGEN;

ANGIOGENESIS; APOPTOSIS; BIOLOGICAL PHENOMENA AND FUNCTIONS CONCERNING THE ENTIRE ORGANISM; BIOSYNTHESIS; CANCER GROWTH; CARBOHYDRATE METABOLISM; CARCINOGENESIS; CATABOLISM; CELL DIVISION; CELL HYPOXIA; CELL METABOLISM; CELL PROLIFERATION; CELL STRESS; CELL TRANSPORT; CITRIC ACID CYCLE; ENERGY METABOLISM; ENVIRONMENTAL EXPOSURE; ENVIRONMENTAL FACTOR; EPIGENETICS; GENE EXPRESSION; GENOMIC INSTABILITY; GLYCOLYSIS; HUMAN; HYPOXIA; IMMUNE EVASION; INFLAMMATION; INTRACELLULAR SIGNALING; LIPID METABOLISM; LIPOGENESIS; LIPOLYSIS; MALIGNANT NEOPLASTIC DISEASE; METABOLIC DISORDER; METABOLIC REPROGRAMMING; METABOLITE; METASTASIS; NONHUMAN; NUTRITION; OXIDATIVE STRESS; PHYSICAL STRESS; PRIORITY JOURNAL; PROTEIN METABOLISM; REGULATORY MECHANISM; REVIEW; RISK ASSESSMENT; SELECTION BIAS; SIGNAL TRANSDUCTION; TOXICOLOGY; TUMOR INVASION; ADVERSE EFFECTS; ANIMAL; CHEMICALLY INDUCED; METABOLISM; NEOPLASMS;

ANIMALS; CARCINOGENESIS; CARCINOGENS, ENVIRONMENTAL; ENVIRONMENTAL EXPOSURE; HUMANS; NEOPLASMS;

EID: 84937720481     PISSN: 01433334     EISSN: 14602180     Source Type: Journal    
DOI: 10.1093/carcin/bgv037     Document Type: Review

References (292)

1. Doll, R. et al. (1981) The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J. Natl. Cancer Inst., 66, 1191-1308.
2. Colditz, G.A. et al. (2012) Preventability of cancer: the relative contributions of biologic and social and physical environmental determinants of cancer mortality. Annu. Rev. Public Health, 33, 137-156.
3. Hanahan, D. et al. (2011) Hallmarks of cancer: the next generation. Cell, 144, 646-674.
4. Floor, S.L. et al. (2012) Hallmarks of cancer: of all cancer cells, all the time? Trends Mol. Med., 18, 509-515.
5. Warburg, O. (ed.) (1930) The Metabolism of Tumours: Investigations from the Kaiser Wilhelm Institute for Biology, Berlin-Dahlen. Constable & Company Limited, London.
6. Aisenberg, A.C. (1961) The Glycolysis and Respiration of Tumors. Academic Press, New York.
7. Weinhouse, S. (1976) The Warburg hypothesis fifty years later. Z. Krebsforsch. Klin. Onkol. Cancer Res. Clin. Oncol., 87, 115-126.
8. Racker, E. (1976) A New Look at Mechanisms in Bioenergetics. Academic Press, New York.
9. Dickens, F. et al. (1933) The metabolism of normal and tumour tissue: the effects of lactate, pyruvate and deprivation of substrate. Biochem. J., 27, 1134-1140.
10. Dickens, F. et al. (1933) Metabolism of normal and tumour tissue: ammonia and urea formation. Biochem. J., 27, 1123-1133.
11. Warburg, O. (1956) On the origin of cancer cells. Science, 123, 309-314.
12. Robey, R.B. (2011) On Dogma and the Metabolic Gestalt of Tumor Cells. Science, E-Letter. www.sciencemag.org/content/330/6009/1338/reply (2 May 2015, date last accessed).
13. Newsholme, E.A. et al. (1991) Application of metabolic-control logic to fuel utilization and its significance in tumor cells. Adv. Enzyme Regul., 31, 225-246.
14. Dickens, F. et al. (1930) The metabolism of normal and tumour tissue: The respiratory quotient, and the relationship of respiration to glycolysis. Biochem. J., 24, 1301-1326.
15. Lazebnik, Y. (2010) What are the hallmarks of cancer? Nat. Rev. Cancer, 10, 232-233.
16. Cantor, J.R. et al. (2012) Cancer cell metabolism: one hallmark, many faces. Cancer Discov., 2, 881-898.
17. Vandenberg, L.N. et al. (2012) Hormones and endocrine-disrupting chemicals: low-dose effects and nonmonotonic dose responses. Endocr. Rev., 33, 378-455.
18. Myers, J.P. et al. (2009) A clash of old and new scientific concepts in toxicity, with important implications for public health. Environ. Health Perspect., 117, 1652-1655.
19. Rudel, R.A. et al. (2007) Chemicals causing mammary gland tumors in animals signal new directions for epidemiology, chemicals testing, and risk assessment for breast cancer prevention. Cancer, 109(12 Suppl), 2635-2666.
20. Goodson, W.H., et al. (2015) Assessing the carcinogenic potential of low dose exposures to chemical mixtures in the environment: The challenge ahead. Carcinogenesis, This issue.
21. DeBerardinis, R.J. et al. (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab., 7, 11-20.
22. Hu, J. et al. (2013) Heterogeneity of tumor-induced gene expression changes in the human metabolic network. Nat. Biotechnol., 31, 522-529.
23. Robey, R.B. et al. (2006) Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt. Oncogene, 25, 4683-4696.
24. Vander Heiden, M.G. et al. (2009) Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science, 324, 1029-1033.
25. Lowry, O.H. et al. (1964) The relationships between substrates and enzymes of glycolysis in brain. J. Biol. Chem., 239, 31-42.
26. Locasale, J.W. et al. (2011) Metabolic flux and the regulation of mammalian cell growth. Cell Metab., 14, 443-451.
27. Samudio, I. et al. (2009) Mitochondrial uncoupling and the Warburg effect: molecular basis for the reprogramming of cancer cell metabolism. Cancer Res., 69, 2163-2166.
28. Baffy, G. et al. (2011) Mitochondrial recoupling: a novel therapeutic strategy for cancer? Br. J. Cancer, 105, 469-474.
29. Lawrence, M.S. et al. (2013) Mutational heterogeneity in cancer and the search for new cancer-associated genes. Nature, 499, 214-218.
30. Smith, D.G. et al. (2013) Parallels between embryo and cancer cell metabolism. Biochem. Soc. Trans., 41, 664-669.
31. Crabtree, H.G. (1929) Observations on the carbohydrate metabolism of tumours. Biochem. J., 23, 536-545.
32. Ibsen, K.H. (1961) The Crabtree effect: a review. Cancer Res., 21, 829-841.
33. Robey, R.B. et al. (2005) Mitochondrial hexokinases: guardians of the mitochondria. Cell Cycle, 4, 654-658.
34. Robey, R.B. et al. (2009) Is Akt the "Warburg kinase"?-Akt-energy metabolism interactions and oncogenesis. Semin. Cancer Biol., 19, 25-31.
35. Wilson, J.E. (1995) Hexokinases. Rev. Physiol. Biochem. Pharmacol., 126, 65-198.
36. Wilson, J.E. (1997) An introduction to the isoenzymes of mammalian hexokinase types I-III. Biochem. Soc. Trans., 25, 103-107.
37. Wilson, J.E. (2003) Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function. J. Exp. Biol., 206(Pt 12), 2049-2057.
38. Patra, K.C. et al. (2013) Hexokinase 2 is required for tumor initiation and maintenance and its systemic deletion is therapeutic in mouse models of cancer. Cancer Cell, 24, 213-228.
39. Warburg, O. et al. (1970) [Genesis of tumor metabolism by vitamin B1 deficiency (thiamine deficiency)]. Z. Naturforsch. B., 25, 332-333.
40. Medes, G. et al. (1958) Metabolism of neoplastic tissue. XIII. Substrate competition in fatty acid oxidation in ascites tumor cells. Cancer Res., 18, 352-359.
41. Horecker, B.L. (2002) The pentose phosphate pathway. J. Biol. Chem., 277, 47965-47971.
42. Le Goffe, C. et al. (2002) Metabolic control of resistance of human epithelial cells to H2O2 and NO stresses. Biochem. J., 364(Pt 2), 349-359.
43. Nutt, L.K. et al. (2005) Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2. Cell, 123, 89-103.
44. Andersen, J.L. et al. (2013) The tangled circuitry of metabolism and apoptosis. Mol. Cell, 49, 399-410.
45. Wellen, K.E. et al. (2010) The hexosamine biosynthetic pathway couples growth factor-induced glutamine uptake to glucose metabolism. Genes Dev., 24, 2784-2799.
46. Ying, H. et al. (2012) Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell, 149, 656-670.
47. Guillaumond, F. et al. (2013) Strengthened glycolysis under hypoxia supports tumor symbiosis and hexosamine biosynthesis in pancreatic adenocarcinoma. Proc. Natl Acad. Sci. USA, 110, 3919-3924.
48. Ma, Z. et al. (2013) O-GlcNAc in cancer biology. Amino Acids, 45, 719-733.
49. Ruan, H.B. et al. (2013) Cracking the O-GlcNAc code in metabolism. Trends Endocrinol. Metab., 24, 301-309.
50. Owen, O.E. et al. (2002) The key role of anaplerosis and cataplerosis for citric acid cycle function. J. Biol. Chem., 277, 30409-30412.
51. Kalhan, S.C. et al. (2012) Resurgence of serine: an often neglected but indispensable amino Acid. J. Biol. Chem., 287, 19786-19791.
52. Young, C.D. et al. (2008) Sugar and fat-that's where it's at: metabolic changes in tumors. Breast Cancer Res., 10, 202.
53. Kuemmerle, N.B. et al. (2011) Lipoprotein lipase links dietary fat to solid tumor cell proliferation. Mol. Cancer Ther., 10, 427-436.
54. Menendez, J.A. et al. (2007) Fatty acid synthase and the lipogenic phenotype in cancer pathogenesis. Nat. Rev. Cancer, 7, 763-777.
55. Rysman, E. et al. (2010) De novo lipogenesis protects cancer cells from free radicals and chemotherapeutics by promoting membrane lipid saturation. Cancer Res., 70, 8117-8126.
56. Mashima, T. et al. (2009) De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. Br. J. Cancer, 100, 1369-1372.
57. Metallo, C.M. et al. (2012) Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia. Nature, 481, 380-384.
58. Hatzivassiliou, G. et al. (2005) ATP citrate lyase inhibition can suppress tumor cell growth. Cancer Cell, 8, 311-321.
59. Galdieri, L. et al. (2012) Acetyl-CoA carboxylase regulates global histone acetylation. J. Biol. Chem., 287, 23865-23876.
60. Kamphorst, J.J. et al. (2013) Hypoxic and Ras-transformed cells support growth by scavenging unsaturated fatty acids from lysophospholipids. Proc. Natl Acad. Sci. USA., 110, 8882-8887.
61. Semenza, G.L. (2013) HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J. Clin. Invest., 123, 3664-3671.
62. Nomura, D.K. et al. (2010) Monoacylglycerol lipase regulates a fatty acid network that promotes cancer pathogenesis. Cell, 140, 49-61.
63. Goldberg, I.J. et al. (2009) Regulation of fatty acid uptake into tissues: lipoprotein lipase- and CD36-mediated pathways. J. Lipid Res., 50 Suppl, S86-S90.
64. Hale, J.S. et al. (2014) Cancer stem cell-specific scavenger receptor CD 36 drives glioblastoma progression. Stem Cells, 32, 1746-1758.
65. Louie, S.M. et al. (2013) Cancer cells incorporate and remodel exogenous palmitate into structural and oncogenic signaling lipids. Biochim. Biophys. Acta, 1831, 1566-1572.
66. Weidberg, H. et al. (2009) Lipophagy: selective catabolism designed for lipids. Dev. Cell, 16, 628-630.
67. Singh, R. et al. (2012) Lipophagy: connecting autophagy and lipid metabolism. Int. J. Cell Biol., 2012, 282041.
68. Christian, P. et al. (2013) Autophagy: emerging roles in lipid homeostasis and metabolic control. Biochim. Biophys. Acta, 1831, 819-824.
69. Chajès, V. et al. (2006) Acetyl-CoA carboxylase alpha is essential to breast cancer cell survival. Cancer Res., 66, 5287-5294.
70. Lepage, G.A. et al. (1960) Biochemistry of tumors. Prog. Exp. Tumor Res., 1, 440-476.
71. Guo, J.Y. et al. (2011) Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev., 25, 460-470.
72. Liu, E.Y. et al. (2012) Autophagy and cancer-issues we need to digest. J. Cell Sci., 125(Pt 10), 2349-2358.
73. Possemato, R. et al. (2011) Functional genomics reveal that the serine synthesis pathway is essential in breast cancer. Nature, 476, 346-350.
74. Locasale, J.W. (2013) Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat. Rev. Cancer, 13, 572-583.
75. Yun, J. et al. (2012) Interactions between epigenetics and metabolism in cancers. Front. Oncol., 2, 163.
76. Balasubramanian, M.N. et al. (2013) Asparagine synthetase: regulation by cell stress and involvement in tumor biology. Am. J. Physiol. Endocrinol. Metab., 304, E789-E799.
77. DeBerardinis, R.J. et al. (2010) Q's next: the diverse functions of glutamine in metabolism, cell biology and cancer. Oncogene, 29, 313-324.
78. Hensley, C.T. et al. (2013) Glutamine and cancer: cell biology, physiology, and clinical opportunities. J. Clin. Invest., 123, 3678-3684.
79. Newsholme, E.A. et al. (1985) The role of high rates of glycolysis and glutamine utilization in rapidly dividing cells. Biosci. Rep., 5, 393-400.
80. Meyerhof, O. (1951) Mechanisms of glycolysis and fermentation. Can. J. Med. Sci., 29, 63-77.
81. Warburg, O. et al. (1958) [Partial anaerobiosis and radiation-sensitivity of cancer cells]. Arch. Biochem. Biophys., 78, 573-586.
82. Atkinson, D.E. (1965) Biological feedback control at the molecular level. Science, 150, 851-857.
83. Racker, E. et al. (1983) The role of ATPase in glycolysis of Ehrlich ascites tumor cells. J. Biol. Chem., 258, 3702-3705.
84. Atkinson, D.E. et al. (1967) Adenosine triphosphate conservation in metabolic regulation. Rat liver citrate cleavage enzyme. J. Biol. Chem., 242, 3239-3241.
85. Hardie, D.G. (2000) Metabolic control: a new solution to an old problem. Curr. Biol., 10, R757-R759.
86. Alberghina, L. et al. (2012) Cancer cell growth and survival as a systemlevel property sustained by enhanced glycolysis and mitochondrial metabolic remodeling. Front. Physiol., 3, 362.
87. Whitesell, R.R. et al. (2003) Control of glucose phosphorylation in L6 myotubes by compartmentalization, hexokinase, and glucose transport. Biochem. J., 370(Pt 1), 47-56.
88. Whitesell, R.R. et al. (2005) Compartmentalization of transport and phosphorylation of glucose in a hepatoma cell line. Biochem. J., 386(Pt 2), 245-253.
89. Wallace, D.C. (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu. Rev. Genet., 39, 359-407.
90. O'Donnell-Tormey, J. et al. (1987) Secretion of pyruvate. An antioxidant defense of mammalian cells. J. Exp. Med., 165, 500-514.
91. Nath, K.A. et al. (1995) alpha-Ketoacids scavenge H2O2 in vitro and in vivo and reduce menadione-induced DNA injury and cytotoxicity. Am. J. Physiol., 268(1 Pt 1), C227-C236.
92. Herz, H. et al. (1997) Multicomponent investigations of the hydrogen peroxide- and hydroxyl radical-scavenging antioxidant capacities of biofluids: the roles of endogenous pyruvate and lactate. Relevance to inflammatory joint diseases. Free Radic. Res., 26, 19-35.
93. Brand, K.A. et al. (1997) Aerobic glycolysis by proliferating cells: a protective strategy against reactive oxygen species. FASEB J., 11, 388-395.
94. Groussard, C. et al. (2000) Free radical scavenging and antioxidant effects of lactate ion: an in vitro study. J. Appl. Physiol. (1985)., 89, 169-175.
95. Huang, C.Y. et al. (2013) Resistance to hypoxia-induced necroptosis is conferred by glycolytic pyruvate scavenging of mitochondrial superoxide in colorectal cancer cells. Cell Death Dis., 4, e622.
96. Newsholme, E.A. et al. (1973) Regulation in Metabolism. Wiley, London, New York.
97. Hart, G.W. (1997) Dynamic O-linked glycosylation of nuclear and cytoskeletal proteins. Annu. Rev. Biochem., 66, 315-335.
98. Graves, J.D. et al. (1999) Protein phosphorylation and signal transduction. Pharmacol. Ther., 82, 111-121.
99. Mellert, H.S. et al. (2009) Biochemical pathways that regulate acetyltransferase and deacetylase activity in mammalian cells. Trends Biochem. Sci., 34, 571-578.
100. Dang, L. et al. (2009) Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature, 462, 739-744.
101. Le, A. et al. (2012) Glucose-independent glutamine metabolism via TCA cycling for proliferation and survival in B cells. Cell Metab., 15, 110-121.
102. Starkov, A.A. (2008) The role of mitochondria in reactive oxygen species metabolism and signaling. Ann. N. Y. Acad. Sci., 1147, 37-52.
103. Ahlborn, G.J. et al. (2009) Early alterations in protein and gene expression in rat kidney following bromate exposure. Food Chem. Toxicol., 47, 1154-1160.
104. Nath, K.A. et al. (1994) Effect of pyruvate on oxidant injury to isolated and cellular DNA. Kidney Int., 45, 166-176.
105. Chandel, N.S. et al. (2000) Reactive oxygen species generated at mitochondrial complex III stabilize hypoxia-inducible factor-1alpha during hypoxia: a mechanism of O2 sensing. J. Biol. Chem., 275, 25130-25138.
106. Stone, J.R. et al. (2006) Hydrogen peroxide: a signaling messenger. Antioxid. Redox Signal., 8, 243-270.
107. Dang, C.V. et al. (1999) Oncogenic alterations of metabolism. Trends Biochem. Sci., 24, 68-72.
108. Newsholme, E.A., et al. (1983) Biochemistry for the Medical Sciences. Wiley, Chichester; New York.
109. Goldblatt, H. et al. (1953) Induced malignancy in cells from rat myocardium subjected to intermittent anaerobiosis during long propagation in vitro. J. Exp. Med., 97, 525-552.
110. Boucher, Y. et al. (1992) Microvascular pressure is the principal driving force for interstitial hypertension in solid tumors: implications for vascular collapse. Cancer Res., 52, 5110-5114.
111. Ariffin, A.B. et al. (2014) Releasing pressure in tumors: what do we know so far and where do we go from here? A review. Cancer Res., 74, 2655-2662.
112. Weiss, L. (1996) Metastatic inefficiency: intravascular and intraperitoneal implantation of cancer cells. Cancer Treat. Res., 82, 1-11.
113. Barnes, J.M. et al. (2012) Resistance to fluid shear stress is a conserved biophysical property of malignant cells. PLoS One, 7, e50973.
114. McNeil, P.L. et al. (2005) An emergency response team for membrane repair. Nat. Rev. Mol. Cell Biol., 6, 499-505.
115. Jaiswal, J.K. et al. (2014) S100A11 is required for efficient plasma membrane repair and survival of invasive cancer cells. Nat. Commun., 5, 3795.
116. Bernard, C. (1974) Lectures on the Phenomena of Life Common to Animals and Plants. Thomas, Springfield, IL.
117. Robergs, R.A. et al. (2004) Biochemistry of exercise-induced metabolic acidosis. Am. J. Physiol. Regul. Integr. Comp. Physiol., 287, R502-R516.
118. Helmlinger, G. et al. (2002) Acid production in glycolysis-impaired tumors provides new insights into tumor metabolism. Clin. Cancer Res., 8, 1284-1291.
119. Chiche, J. et al. (2010) Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer. J. Cell. Mol. Med., 14, 771-794.
120. Helmlinger, G. et al. (1997) Interstitial pH and pO2 gradients in solid tumors in vivo: high-resolution measurements reveal a lack of correlation. Nat. Med., 3, 177-182.
121. Newell, K. et al. (1993) Studies with glycolysis-deficient cells suggest that production of lactic acid is not the only cause of tumor acidity. Proc. Natl Acad. Sci. USA, 90, 1127-1131.
122. Yamagata, M. et al. (1998) The contribution of lactic acid to acidification of tumours: studies of variant cells lacking lactate dehydrogenase. Br. J. Cancer, 77, 1726-1731.
123. Hay, N. et al. (2004) Upstream and downstream of mTOR. Genes Dev., 18, 1926-1945.
124. Dang, C.V. (2011) Therapeutic targeting of Myc-reprogrammed cancer cell metabolism. Cold Spring Harb. Symp. Quant. Biol., 76, 369-374.
125. Berkers, C.R. et al. (2013) Metabolic regulation by p53 family members. Cell Metab., 18, 617-633.
126. Muller, P.A. et al. (2013) p53 mutations in cancer. Nat. Cell Biol., 15, 2-8.
127. Hanahan, D. et al. (2000) The hallmarks of cancer. Cell, 100, 57-70.
128. Malins, D.C. et al. (1995) The etiology and prediction of breast cancer. Fourier transform-infrared spectroscopy reveals progressive alterations in breast DNA leading to a cancer-like phenotype in a high proportion of normal women. Cancer, 75, 503-517.
129. Weisz, J. et al. (2012) Identification of mammary epithelial cells subject to chronic oxidative stress in mammary epithelium of young women and teenagers living in USA: implication for breast carcinogenesis. Cancer Biol. Ther., 13, 101-113.
130. Anderson, K.M. et al. (2006) Structural alterations in breast stromal and epithelial DNA: the influence of 8,5′-cyclo-2′-deoxyadenosine. Cell Cycle, 5, 1240-1244.
131. Malins, D.C. et al. (2004) Development of a cancer DNA phenotype prior to tumor formation. Proc. Natl Acad. Sci. USA, 101, 10721-10725.
132. Ericson, N.G. et al. (2012) Decreased mitochondrial DNA mutagenesis in human colorectal cancer. PLoS Genet., 8, e1002689.
133. Brewer, G.J. (2010) Epigenetic oxidative redox shift (EORS) theory of aging unifies the free radical and insulin signaling theories. Exp. Gerontol., 45, 173-179.
134. Hiyama, E. et al. (2002) Clinical utility of telomerase in cancer. Oncogene, 21, 643-649.
135. Bagheri, S. et al. (2006) Genes and pathways downstream of telomerase in melanoma metastasis. Proc. Natl Acad. Sci. USA, 103, 11306-11311.
136. Kovalenko, O.A. et al. (2010) A mutant telomerase defective in nuclearcytoplasmic shuttling fails to immortalize cells and is associated with mitochondrial dysfunction. Aging Cell, 9, 203-219.
137. Newsholme, E.A. et al. (1993) The regulatory, informational, and immunomodulatory roles of fat fuels. Am. J. Clin. Nutr., 57(5 Suppl), 738S-750S; discussion 750S.
138. MacIver, N.J. et al. (2013) Metabolic regulation of T lymphocytes. Annu. Rev. Immunol., 31, 259-283.
139. McGettrick, A.F. et al. (2013) How metabolism generates signals during innate immunity and inflammation. J. Biol. Chem., 288, 22893-22898.
140. Kominsky, D.J. et al. (2010) Metabolic shifts in immunity and inflammation. J. Immunol., 184, 4062-4068.
141. Angelini, G. et al. (2002) Antigen-presenting dendritic cells provide the reducing extracellular microenvironment required for T lymphocyte activation. Proc. Natl Acad. Sci. USA, 99, 1491-1496.
142. Swann, J.B. et al. (2007) Immune surveillance of tumors. J. Clin. Invest., 117, 1137-1146.
143. Tannahill, G.M. et al. (2013) Succinate is an inflammatory signal that induces IL-1β through HIF-1α. Nature, 496, 238-242.
144. Taneja, N. et al. (2004) Proinflammatory interleukin-1 cytokines increase mesangial cell hexokinase activity and hexokinase II isoform abundance. Am. J. Physiol. Cell Physiol., 287, C548-C557.
145. Yea, K. et al. (2008) Lysophosphatidic acid regulates blood glucose by stimulating myotube and adipocyte glucose uptake. J. Mol. Med. (Berl)., 86, 211-220.
146. Ando, M. et al. (2010) Interleukin 6 enhances glycolysis through expression of the glycolytic enzymes hexokinase 2 and 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3. J. Nippon Med. Sch., 77, 97-105.
147. Straus, D.S. (2013) TNFα and IL-17 cooperatively stimulate glucose metabolism and growth factor production in human colorectal cancer cells. Mol. Cancer, 12, 78.
148. Mazurek, S. et al. (2001) Effects of the human papilloma virus HPV-16 E7 oncoprotein on glycolysis and glutaminolysis: role of pyruvate kinase type M2 and the glycolytic-enzyme complex. Biochem. J., 356(Pt 1), 247-256.
149. Hsu, P.P. et al. (2008) Cancer cell metabolism: Warburg and beyond. Cell, 134, 703-707.
150. Noch, E. et al. (2012) Oncogenic viruses and tumor glucose metabolism: like kids in a candy store. Mol. Cancer Ther., 11, 14-23.
151. Vogelstein, B. et al. (2000) Surfing the p53 network. Nature, 408, 307-310.
152. Dang, C.V. (2012) MYC on the path to cancer. Cell, 149, 22-35.
153. Futreal, P.A. et al. (2004) A census of human cancer genes. Nat. Rev. Cancer, 4, 177-183.
154. De Coster, S. et al. (2012) Endocrine-disrupting chemicals: associated disorders and mechanisms of action. J. Environ. Public Health, 2012, 713696.
155. Ramanathan, A. et al. (2005) Perturbational profiling of a cell-line model of tumorigenesis by using metabolic measurements. Proc. Natl Acad. Sci. USA, 102, 5992-5997.
156. Gaglio, D. et al. (2011) Oncogenic K-Ras decouples glucose and glutamine metabolism to support cancer cell growth. Mol. Syst. Biol., 7, 523.
157. Chiaradonna, F. et al. (2006) Expression of transforming K-Ras oncogene affects mitochondrial function and morphology in mouse fibroblasts. Biochim. Biophys. Acta, 1757, 1338-1356.
158. Dang, C.V. et al. (2006) The c-Myc target gene network. Semin. Cancer Biol., 16, 253-264.
159. Jones, R.G. et al. (2005) AMP-activated protein kinase induces a p53-dependent metabolic checkpoint. Mol. Cell, 18, 283-293.
160. Jänicke, R.U. et al. (2009) The do's and don'ts of p53 isoforms. Biol. Chem., 390, 951-963.
161. Cheung, E.C. et al. (2013) TIGAR is required for efficient intestinal regeneration and tumorigenesis. Dev. Cell, 25, 463-477.
162. Gerin, I. et al. (2014) Identification of TP53-induced glycolysis and apoptosis regulator (TIGAR) as the phosphoglycolate-independent 2,3-bisphosphoglycerate phosphatase. Biochem. J., 458, 439-448.
163. Cheung, E.C. et al. (2012) Mitochondrial localization of TIGAR under hypoxia stimulates HK2 and lowers ROS and cell death. Proc. Natl Acad. Sci. USA, 109, 20491-20496.
164. Assaily, W. et al. (2011) ROS-mediated p53 induction of Lpin1 regulates fatty acid oxidation in response to nutritional stress. Mol. Cell, 44, 491-501.
165. Maiuri, M.C. et al. (2010) Autophagy regulation by p53. Curr. Opin. Cell Biol., 22, 181-185.
166. Bao, Y. et al. (2013) Energy management by enhanced glycolysis in G1 phase in human colon cancer cells in vivo and in vitro. Mol Cancer Res., 11, 973-985.
167. Bell, E.L. et al. (2007) The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production. J. Cell Biol., 177, 1029-1036.
168. Talmadge, J.E. et al. (2010) AACR centennial series: the biology of cancer metastasis: historical perspective. Cancer Res., 70, 5649-5669.
169. Fidler, I.J. (2002) The organ microenvironment and cancer metastasis. Differentiation, 70, 498-505.
170. Grassian, A.R. et al. (2011) Extracellular matrix regulation of metabolism and implications for tumorigenesis. Cold Spring Harb. Symp. Quant. Biol., 76, 313-324.
171. Wallace, D.C. et al. (2010) Mitochondrial energetics and therapeutics. Annu. Rev. Pathol., 5, 297-348.
172. Nadeau, J.H. (2009) Transgenerational genetic effects on phenotypic variation and disease risk. Hum. Mol. Genet., 18(R2), R202-R210.
173. Johnson, C. et al. (2015) Epigenetics and cancer metabolism. Cancer Lett., 356(2 Pt A), 309-314.
174. Bungard, D. et al. (2010) Signaling kinase AMPK activates stress-promoted transcription via histone H2B phosphorylation. Science, 329, 1201-1205.
175. Esteller, M. (2007) Cancer epigenomics: DNA methylomes and histone-modification maps. Nat. Rev. Genet., 8, 286-298.
176. Latham, T. et al. (2012) Lactate, a product of glycolytic metabolism, inhibits histone deacetylase activity and promotes changes in gene expression. Nucleic Acids Res., 40, 4794-4803.
177. Du, X.L. et al. (2000) Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation. Proc. Natl Acad. Sci. USA, 97, 12222-12226.
178. Xu, Q. et al. (2014) AMPK regulates histone H2B O-GlcNAcylation. Nucleic Acids Res., 42, 5594-5604.
179. Pegg, A.E. (1986) Recent advances in the biochemistry of polyamines in eukaryotes. Biochem. J., 234, 249-262.
180. Hue, L. et al. (1993) Fructose 2,6-bisphosphate and the control of glycolysis by growth factors, tumor promoters and oncogenes. Adv. Enzyme Regul., 33, 97-110.
181. Yalcin, A. et al. (2009) Regulation of glucose metabolism by 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases in cancer. Exp. Mol. Pathol., 86, 174-179.
182. Chaneton, B. et al. (2012) Rocking cell metabolism: revised functions of the key glycolytic regulator PKM2 in cancer. Trends Biochem. Sci., 37, 309-316.
183. Vander Heiden, M.G. et al. (2011) Metabolic pathway alterations that support cell proliferation. Cold Spring Harb. Symp. Quant. Biol., 76, 325-334.
184. Luo, W. et al. (2012) Emerging roles of PKM2 in cell metabolism and cancer progression. Trends Endocrinol. Metab., 23, 560-566.
185. Vander Heiden, M.G. et al. (2010) Evidence for an alternative glycolytic pathway in rapidly proliferating cells. Science, 329, 1492-1499.
186. Gui, D.Y. et al. (2013) Allosteric regulation of PKM2 allows cellular adaptation to different physiological states. Sci. Signal., 6, pe7.
187. Shim, H. et al. (1997) c-Myc transactivation of LDH-A: implications for tumor metabolism and growth. Proc. Natl Acad. Sci. USA, 94, 6658-6663.
188. Fantin, V.R. et al. (2006) Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell, 9, 425-434.
189. Horecker, B.L. (1976) The biochemistry of sugars. Int. Z. Vitam. Ernahrungsforsch. Beih., 15, 1-21.
190. Schwartz, A.G. et al. (1995) Mechanism of cancer preventive action of DHEA. Role of glucose-6-phosphate dehydrogenase. Ann. N. Y. Acad. Sci., 774, 180-186.
191. Adam, J. et al. (2013) Rare insights into cancer biology. Oncogene.
192. Cairns, R.A. et al. (2013) Oncogenic isocitrate dehydrogenase mutations: mechanisms, models, and clinical opportunities. Cancer Discov., 3, 730-741.
193. Losman, J.A. et al. (2013) What a difference a hydroxyl makes: mutant IDH, ®-2-hydroxyglutarate, and cancer. Genes Dev., 27, 836-852.
194. Rohle, D. et al. (2013) An inhibitor of mutant IDH1 delays growth and promotes differentiation of glioma cells. Science, 340, 626-630.
195. Mullen, A.R. et al. (2012) Genetically-defined metabolic reprogramming in cancer. Trends Endocrinol. Metab., 23, 552-559.
196. Notarnicola, M. et al. (2012) A significant role of lipogenic enzymes in colorectal cancer. Anticancer Res., 32, 2585-2590.
197. Zaidi, N. et al. (2013) Lipogenesis and lipolysis: the pathways exploited by the cancer cells to acquire fatty acids. Prog. Lipid Res., 52, 585-589.
198. Young, S.G. et al. (2013) Biochemistry and pathophysiology of intravascular and intracellular lipolysis. Genes Dev., 27, 459-484.
199. Locasale, J.W. et al. (2011) Phosphoglycerate dehydrogenase diverts glycolytic flux and contributes to oncogenesis. Nat. Genet., 43, 869-874.
200. Santidrian, A.F. et al. (2013) Mitochondrial complex I activity and NAD+/NADH balance regulate breast cancer progression. J. Clin. Invest., 123, 1068-1081.
201. Boyd, J. et al. (2011) Exploring the boundaries of additivity: mixtures of NADH: quinone oxidoreductase inhibitors. Chem. Res. Toxicol., 24, 1242-1250.
202. Erusalimsky, J.D. et al. (2007) Nitric oxide and mitochondrial signaling: from physiology to pathophysiology. Arterioscler. Thromb. Vasc. Biol., 27, 2524-2531.
203. Szablewski, L. (2013) Expression of glucose transporters in cancers. Biochim. Biophys. Acta, 1835, 164-169.
204. Bolaños, J.P. (2014) TIGAR's promiscuity. Biochem. J., 458, e5-e7.
205. Marsin, A.S. et al. (2000) Phosphorylation and activation of heart PFK-2 by AMPK has a role in the stimulation of glycolysis during ischaemia. Curr. Biol., 10, 1247-1255.
206. Etchegaray, J.-P. et al. (2013) The histone deacetylase SIRT6: at the crossroads between epigenetics, metabolism and disease. Curr. Top. Med. Chem., 13, 2991-3000.
207. Feldman, J.L. et al. (2013) Activation of the protein deacetylase SIRT6 by long-chain fatty acids and widespread deacylation by mammalian sirtuins. J. Biol. Chem., 288, 31350-31356.
208. Wu, S. et al. (2013) Dual roles of PKM2 in cancer metabolism. Acta Biochim. Biophys. Sin. (Shanghai)., 45, 27-35.
209. Copley, S.D. (2012) Moonlighting is mainstream: paradigm adjustment required. Bioessays, 34, 578-588.
210. Luo, W. et al. (2011) Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell, 145, 732-744.
211. Gao, X. et al. (2012) Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. Mol. Cell, 45, 598-609.
212. Reitman, Z.J. et al. (2010) Isocitrate dehydrogenase 1 and 2 mutations in cancer: alterations at a crossroads of cellular metabolism. J. Natl Cancer Inst., 102, 932-941.
213. Lu, C. et al. (2012) IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature, 483, 474-478.
214. Pirozzi, C.J. et al. (2013) Releasing the block: setting differentiation free with mutant IDH inhibitors. Cancer Cell, 23, 570-572.
215. Morris, S.M. Jr. (2007) Arginine metabolism: boundaries of our knowledge. J. Nutr., 137(6 Suppl 2), 1602S-1609S.
216. Rasola, A. et al. (2010) Signal transduction to the permeability transition pore. FEBS Lett., 584, 1989-1996.
217. Srere, P.A. (1987) Complexes of sequential metabolic enzymes. Annu. Rev. Biochem., 56, 89-124.
218. Deitmer, J.W. et al. (2013) Transport metabolons with carbonic anhydrases. Front. Physiol., 4, 291.
219. Lapuente-Brun, E. et al. (2013) Supercomplex assembly determines electron flux in the mitochondrial electron transport chain. Science, 340, 1567-1570.
220. Schägger, H. et al. (2000) Supercomplexes in the respiratory chains of yeast and mammalian mitochondria. EMBO J., 19, 1777-1783.
221. Baracca, A. et al. (2010) Mitochondrial complex I decrease is responsible for bioenergetic dysfunction in K-ras transformed cells. Biochim. Biophys. Acta, 1797, 314-323.
222. Collarini, E.J. et al. (1987) Mechanisms of transport of amino acids across membranes. Annu. Rev. Nutr., 7, 75-90.
223. Taylor, P.M. (2014) Role of amino acid transporters in amino acid sensing. Am. J. Clin. Nutr., 99, 223S-230S.
224. Vyssokikh, M.Y. et al. (2003) The function of complexes between the outer mitochondrial membrane pore (VDAC) and the adenine nucleotide translocase in regulation of energy metabolism and apoptosis. Acta Biochim. Pol., 50, 389-404.
225. Hardie, D.G. (2014) AMP-activated protein kinase: a key regulator of energy balance with many roles in human disease. J Intern Med.
226. Carling, D. et al. (2012) AMP-activated protein kinase: new regulation, new roles? Biochem. J., 445, 11-27.
227. Dandapani, M. et al. (2013) AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells? Biochem. Soc. Trans., 41, 687-693.
228. Liang, J. et al. (2013) AMPK: a contextual oncogene or tumor suppressor? Cancer Res., 73, 2929-2935.
229. Yeung, F. et al. (2004) Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J., 23, 2369-2380.
230. Preyat, N. et al. (2013) Sirtuin deacylases: a molecular link between metabolism and immunity. J. Leukoc. Biol., 93, 669-680.
231. Kell, D.B. (2004) Metabolomics and systems biology: making sense of the soup. Curr. Opin. Microbiol., 7, 296-307.
232. Giancotti, F.G. (2013) Mechanisms governing metastatic dormancy and reactivation. Cell, 155, 750-764.
233. Wild, C.P. (2005) Complementing the genome with an "exposome": the outstanding challenge of environmental exposure measurement in molecular epidemiology. Cancer Epidemiol. Biomarkers Prev., 14, 1847-1850.
234. Cohen, S.M. et al. (2011) Chemical carcinogenesis. Toxicol. Sci., 120 Suppl 1, S76-S92.
235. Kleinstreuer, N.C. et al. (2013) In vitro perturbations of targets in cancer hallmark processes predict rodent chemical carcinogenesis. Toxicol. Sci., 131, 40-55.
236. Meyer, J.N. et al. (2013) Mitochondria as a target of environmental toxicants. Toxicol. Sci., 134, 1-17.
237. Waddell, B.L. et al. (2001) Agricultural use of organophosphate pesticides and the risk of non-Hodgkin's lymphoma among male farmers (United States). Cancer Causes Control, 12, 509-517.
238. Weichenthal, S. et al. (2010) A review of pesticide exposure and cancer incidence in the Agricultural Health Study cohort. Environ. Health Perspect., 118, 1117-1125.
239. Kapka-Skrzypczak, L. et al. (2011) Biomonitoring and biomarkers of organophosphate pesticides exposure-state of the art. Ann. Agric. Environ. Med., 18, 294-303.
240. Koutros, S. et al. (2013) Risk of total and aggressive prostate cancer and pesticide use in the Agricultural Health Study. Am. J. Epidemiol., 177, 59-74.
241. Alavanja, M.C. et al. (2013) Increased cancer burden among pesticide applicators and others due to pesticide exposure. CA. Cancer J. Clin., 63, 120-142.
242. Abdollahi, M. et al. (2004) Pesticides and oxidative stress: a review. Med. Sci. Monit., 10, RA141-RA147.
243. Lassiter, T.L. et al. (2008) Exposure of neonatal rats to parathion elicits sex-selective reprogramming of metabolism and alters the response to a high-fat diet in adulthood. Environ. Health Perspect., 116, 1456-1462.
244. Quistad, G.B. et al. (2006) Each lipase has a unique sensitivity profile for organophosphorus inhibitors. Toxicol. Sci., 91, 166-172.
245. CDC (2009) Fourth Report on Human Exposure to Environmental Chemicals, 2009. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA.
246. Kale, M. et al. (1999) Lipid peroxidative damage on pyrethroid exposure and alterations in antioxidant status in rat erythrocytes: a possible involvement of reactive oxygen species. Toxicol. Lett., 105, 197-205.
247. Philip, G.H. et al. (1995) Cypermethrin-induced in vivo alterations in the carbohydrate metabolism of freshwater fish, Labeo rohita. Ecotoxicol. Environ. Saf., 31, 173-178.
248. Liang, Y.J. et al. (2013) A metabonomic investigation of the effects of 60 days exposure of rats to two types of pyrethroid insecticides. Chem. Biol. Interact., 206, 302-308.
249. Janiszewski, L. (1990) The action of toxins on the voltage-gated sodium channel. Pol. J. Pharmacol. Pharm., 42, 581-588.
250. Breckenridge, C.B. et al. (2009) Evidence for a separate mechanism of toxicity for the Type I and the Type II pyrethroid insecticides. Neurotoxicology, 30 Suppl 1, S17-S31.
251. LoPachin, R.M. et al. (2012) Molecular mechanism of acrylamide neurotoxicity: lessons learned from organic chemistry. Environ. Health Perspect., 120, 1650-1657.
252. Kasiviswanathan, R. et al. (2013) Translesion synthesis past acroleinderived DNA adducts by human mitochondrial DNA polymerase γ. J. Biol. Chem., 288, 14247-14255.
253. Yadav, U.C. et al. (2013) Aldose reductase regulates acrolein-induced cytotoxicity in human small airway epithelial cells. Free Radic. Biol. Med., 65, 15-25.
254. Saraswat, M. et al. (2006) Overexpression of aldose reductase in human cancer tissues. Med. Sci. Monit., 12, CR525-CR529.
255. Kell, D.B. (2010) Towards a unifying, systems biology understanding of large-scale cellular death and destruction caused by poorly liganded iron: Parkinson's, Huntington's, Alzheimer's, prions, bactericides, chemical toxicology and others as examples. Arch. Toxicol., 84, 825-889.
256. Lee, J.C. et al. (2012) Oxidative stress and metal carcinogenesis. Free Radic. Biol. Med., 53, 742-757.
257. CDC (2013) Fourth Report on Human Exposure to Environmental Chemicals, Updated Tables, (March, 2013). U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Atlanta, GA.
258. Waldron, K.J. et al. (2009) Metalloproteins and metal sensing. Nature, 460, 823-830.
259. Jeon, K.I. et al. (2000) Thiol-reactive metal compounds inhibit NFkappa B activation by blocking I kappa B kinase. J. Immunol., 164, 5981-5989.
260. Zhao, F. et al. (2013) Arsenic exposure induces the Warburg effect in cultured human cells. Toxicol. Appl. Pharmacol., 271, 72-77.
261. Zhao, F. et al. (2014) Arsenite-induced pseudo-hypoxia results in loss of anchorage-dependent growth in BEAS-2B pulmonary epithelial cells. PLoS One, 9, e114549.
262. Pysher, M.D. et al. (2007) Increased hexokinase II expression in the renal glomerulus of mice in response to arsenic. Toxicol. Appl. Pharmacol., 224, 39-48.
263. Byrne, C. et al. (2013) Metals and breast cancer. J. Mammary Gland Biol. Neoplasia, 18, 63-73.
264. Gerlinger, M. et al. (2012) Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med., 366, 883-892.
265. Berridge, M.V. et al. (2010) Metabolic flexibility and cell hierarchy in metastatic cancer. Mitochondrion, 10, 584-588.
266. Ames, B.N. et al. (1990) Nature's chemicals and synthetic chemicals: comparative toxicology. Proc. Natl Acad. Sci. USA, 87, 7782-7786.
267. Rády, P. et al. (1980) Effect of carcinogenic and non-carcinogenic chemicals on the activities of four glycolytic enzymes in mouse lung. Chem. Biol. Interact., 31, 209-213.
268. Knudson, A.G. Jr. (1971) Mutation and cancer: statistical study of retinoblastoma. Proc. Natl Acad. Sci. USA, 68, 820-823.
269. Chowaniec, J. et al. (1974) Proceedings: syncarcinogenesis with n-methyl N-nitrosourea (MNU) and cyclamate in rat urinary bladder. Br. J. Cancer, 30, 180.
270. Hicks, R.M. (1980) Multistage carcinogenesis in the urinary bladder. Br. Med. Bull., 36, 39-46.
271. Meek, M.E. et al. (2003) A framework for human relevance analysis of information on carcinogenic modes of action. Crit. Rev. Toxicol., 33, 591-653.
272. Romanov, S. et al. (2008) Homogeneous reporter system enables quantitative functional assessment of multiple transcription factors. Nat. Methods, 5, 253-260.
273. Martin, M.T. et al. (2010) Impact of environmental chemicals on key transcription regulators and correlation to toxicity end points within EPA's ToxCast program. Chem. Res. Toxicol., 23, 578-590.
274. Collins, F.S. et al. (2008) Toxicology. Transforming environmental health protection. Science, 319, 906-907.
275. Haber, D.A. et al. (2007) Cancer: drivers and passengers. Nature, 446, 145-146.
276. Wheeler, D.A. et al. (2013) From human genome to cancer genome: the first decade. Genome Res., 23, 1054-1062.
277. Forbes, S.A. et al. (2011) COSMIC: mining complete cancer genomes in the Catalogue of Somatic Mutations in Cancer. Nucleic Acids Res., 39(Database issue), D945-D950.
278. Cowper-Sallari, R. et al. (2011) Layers of epistasis: genome-wide regulatory networks and network approaches to genome-wide association studies. Wiley Interdiscip. Rev. Syst. Biol. Med., 3, 513-526.
279. Hiller, K. et al. (2011) Elucidation of cellular metabolism via metabolomics and stable-isotope assisted metabolomics. Curr. Pharm. Biotechnol., 12, 1075-1086.
280. Wang, T. et al. (2014) Genetic screens in human cells using the CRISPR-Cas9 system. Science, 343, 80-84.
281. Sander, J.D. et al. (2014) CRISPR-Cas systems for editing, regulating and targeting genomes. Nat. Biotechnol., 32, 347-355.
282. Shalem, O. et al. (2014) Genome-scale CRISPR-Cas9 knockout screening in human cells. Science, 343, 84-87.
283. Warburg, O. (1956) On respiratory impairment in cancer cells. Science, 124, 269-270.
284. Weinhouse, S. (1956) On respiratory impairment in cancer cells. Science, 124, 267-269.
285. Kielley, R.K. (1957) Inhibitory effect of some aminoazo dyes and other carcinogens on glutamate oxidation in mitochondria of riboflavinedeficient rat liver. J. Natl Cancer Inst., 19, 1077-1085.
286. Dawkins, R. (1989) The Selfish Gene. Oxford University Press, Oxford, New York.
287. Fenton, S.E. (2006) Endocrine-disrupting compounds and mammary gland development: early exposure and later life consequences. Endocrinology, 147(6 Suppl), S18-S24.
288. Soto, A.M. et al. (2013) Does cancer start in the womb? Altered mammary gland development and predisposition to breast cancer due to in utero exposure to endocrine disruptors. J. Mammary Gland Biol. Neoplasia, 18, 199-208.
289. Selikoff, I.J. (1984) Lessons for living in a chemical world. Bull. Environ. Contam. Toxicol., 33, 682-695.
290. Marshall, G. et al. (2007) Fifty-year study of lung and bladder cancer mortality in Chile related to arsenic in drinking water. J. Natl Cancer Inst., 99, 920-928.
291. Steinmaus, C.M. et al. (2013) Drinking water arsenic in northern Chile: high cancer risks 40 years after exposure cessation. Cancer Epidemiol. Biomarkers Prev., 22, 623-630.
292. Bradlow, H.L. et al. (1998) Workshop on hormones, hormone metabolism, the environment, and breast cancer. J. Natl Cancer Inst., 90, 67.