Mechanism of teratogenesis: Electron transfer, reactive oxygen species, and antioxidants

Birth Defects Research Part C - Embryo Today: Reviews

Volumn 78, Issue 4, 2006, Pages 308-325

  Kovacic, Peter ^a   Somanathan, Ratnasamy ^a,b  

^a SAN DIEGO STATE UNIVERSITY   (United States)

^b TIJUANA INSTITUTE OF TECHNOLOGY   (Mexico)

Author keywords

Antioxidants; Electron transfer; Reactive oxygen species; Teratogenesis

Indexed keywords

ALUMINUM; ANTIOXIDANT; ARSENIC; ARSENIC TRIOXIDE; CADMIUM; CELL PROTEIN; CHROMIUM; COPPER; DOMESTIC CHEMICAL; FUNGICIDE; GROUND WATER; HERBICIDE; IMINE; INORGANIC COMPOUND; INSECTICIDE; LEAD; MANGANESE; MERCURY; METAL COMPLEX; NICKEL; ORGANIC COMPOUND; ORGANIC SOLVENT; PENTACHLOROPHENOL; PEROXIDE; QUINONE DERIVATIVE; REACTIVE OXYGEN METABOLITE; SELENIUM; TIN; UNINDEXED DRUG; VANADIUM;

AIR POLLUTION; BEVERAGE; CENTRAL NERVOUS SYSTEM; ELECTRON TRANSPORT; ENZYME INHIBITION; HORMONAL REGULATION; HUMAN; MEMBRANE DAMAGE; MITOCHONDRION; NONHUMAN; OXIDATION REDUCTION REACTION; PRIORITY JOURNAL; RADIATION; REVIEW; TERATOGENESIS; WATER CONTAMINATION;

ABNORMALITIES, DRUG-INDUCED; ABNORMALITIES, RADIATION-INDUCED; ANIMALS; ANTIOXIDANTS; ELECTRON TRANSPORT; FEMALE; HUMANS; METALS; PESTICIDES; PHARMACEUTICAL PREPARATIONS; PREGNANCY; REACTIVE OXYGEN SPECIES; SOLVENTS; TERATOGENS;

EID: 33847633507     PISSN: 1542975X     EISSN: None     Source Type: Journal    
DOI: 10.1002/bdrc.20081     Document Type: Review

References (203)

1. Acharya UR, Mishra M, Tripathy RR, Mishra I. 2006. Testicular dysfunction and antioxidative defense system of Swiss mice after chromic acid exposure. Reprod Toxicol 22:87-91.
2. Adams WJ, Brix KV, Edwards M, et al. 2003. Analysis of field and laboratory data to derive selenium toxicity thresholds for birds. Environ Toxicol Chem 22:2020-2029.
3. Addis A, Moretti ME, Ahmed SF, et al. 2001. Fetal effects of cocaine: an updated meta-analysis. Reprod Toxicol 15:341-369.
4. Alexander P, Tuan RS. 2003. Carbon monoxide-induced axial skeletal dysmorphogenesis in the chick embryo. Birth Defects Res A Clin Mol Teratol 67:219-230.
5. Ames JR, Kovacic P, Kadaba PK, Kiser PF. 1992. Electrochemistry of anticonvulsants: electron transfer as a possible mode of action. Epilepsia 33:936-943.
6. Amicarelli F, Tiboni GM, Colafarina S, et al. 2000. Antioxidant and GSH-related enzyme response to a single teratogenic exposure to the anticonvulsant phenytoin: temporospatial evaluation. Teratology 62:100-107.
7. Anderson D. 2001. Genetic and reproductive toxicity of butadiene and isoprene. Chem Biol Interact 135-136:65-80.
8. Andrade AJM, Grande SW, Talsness CE, et al. 2006. A dose-response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): effects on androgenic status, developmental landmarks and testicular histology in male offspring rats. Toxicology 225:64-74.
9. Aposhian HV, Zakharyan RA, Avram MD, et al. 2004. A review of the enzymology of arsenic metabolism and a new potential role of hydrogen peroxide in the detoxication of the trivalent arsenic species. Toxicol Appl Pharmacol 198:327-335.
10. Aragon MA, Ayala ME, Fortoul TI, et al. 2005. Vanadium induced ultrastructural changes and apoptosis in male germ cells. Reprod Toxicol 20:127-134.
11. Arnon J, Shechtman S, Ornoy A. 2000. The use of psychiatric drugs in pregnancy and lactation. Isr J Psychiatry Relat Sci 37:205-222.
12. Arpino C, Brescianini S, Robert E, et al. 2000. Teratogenic effects of antiepileptic drugs: use of an international database on malformations and drug exposure (MADRE). Epilepsia 41:1436-1443.
13. Aruldhas MM, Subramanian S, Sekar P, et al. 2005. Chronic chromium exposure-induced changes in testicular histoarchitecture are associated with oxidative stress: study in a non-human primate (Macaca radiate Geoffroy). Hum Reprod 20:2801-2813.
14. Bailey B. 2003. Are there teratogenic risks associated with antidotes used in the acute management of poisoned pregnant women? Birth Defects Res A Clin Mol Teratolol 67:133-140.
15. Bailey MM, Boohaker JG, Sawyer RD, et al. 2006. Exposure of pregnant mice to chromium picolinate results in skeletal defects in their offspring. Reprod Toxicol 77:244-249.
16. Bellinger DC. 2005. Teratogen update: lead and pregnancy. Birth Defects Res A Clin Mol Teratol 73:409-420.
17. Bhuller Y, Wells PG. 2006. A developmental role for ataxia telangiectasia mutated (Atm) in protecting the embryo from spontaneous and phenytoin-enhanced embryopathies in culture. Toxicol Sci 93:156-163.
18. Blasiak J, Kowalik J, Małecka-Panas E, et al. 2000. DNA damage and repair in human lymphocytes exposed to three anticancer platinum drugs. Teratog Carcinog Mutagen 20:119-131.
19. Bonnot O, Vollset SE, Godet PF, et al. 2003. In utero exposure to benzodiazepine. Is there a risk for anal atresis with lorazepam? Encephale 29:553-559. [French]
20. Brown K. 2006. Is tamoxifen a genotoxic carcinogen in women? Toxicology 226:27.
21. Bryant PL, Schmid JE, Fenton SE, et al. 2001. Teratogenicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in mice lacking the expression of EGF and/or TGF-alpha. Toxicol Sci 62:103-114.
22. Calderwood TS, Neuman RC, Sawyer DT. 1983. Oxygenation of chloroalkene by superoxide in aprotic media. J Am Chem Soc 105:3337-3339.
23. Cappon GD, Gupta U, Cook JC, et al. 2003. Comparison of the developmental toxicity of aspirin in rabbits when administered throughout organogenesis or during sensitive windows of development. Birth Defects Res B Dev Reprod Toxicol 68:38-46.
24. Chen L, Yang X, Jia H, Zhao B. 2003. Tea catechins protected against lead-induced ROS formation, mitochondrial dysfunction, and calcium dysregulation in PC12 cells. Chem Res Toxicol 16:1155-1161.
25. Chen CS, Wells PG. 2004. In utero origins of cancer. Maternal dietary vitamin E, fetal oxidative DNA damage, and post-natal carcinogenesis in p53 knockout mice. Ann NY Acad Sci 1031:395-398.
26. Chipman JK, Parsons JL, Beddowes EJ. 2006. The multiple influences of glutathione on bromate genotoxicity: Implications for the dose-response relationship. Toxicology 221:187-189.
27. Cohen-Kerem R, Koren G. 2003. Antioxidants and fetal protection against ethanol teratogenicity. Review of the experimental data and implications to humans. Gen Teratol 25:1-9.
28. Crawford PW, Kovacic P, Gilman NW, Ryan MD. 1986. Charge transfer mechanism for benzodiazepine (BZ) action. Correlation of reduction potential of BZ iminium with structure and drug activity. Bioelectrochem Bioenerg 16:407-426.
29. Czeizel AE, Hegedüs S, Tímár L. 1999. Congenital abnormalities and indicators of germinal mutations in the vicinity of an acrylonitrile producing factory. Mutat Res 427:105-123.
30. Czeizel AE, Rockenbauer M, Sørensen HT, Olsen J. 2001. Nitrofurantoin and congenital abnormalities. Eur J Obstet Gynecol Reprod Biol 95:119-126.
31. Dalvie D, Smith E, Deese A, Bowlin S. 2006. In vitro metabolic activation of thiabendazole via 5-hydroxythiabendzole: identification of a conjugate of 5-hydroxythiabendazole. Drug Metab Dispos 34:709-717.
32. Davis GE, Jr, Lowell WE. 2004. The sun determines human longevity: teratogenic effects of chaotic solar radiation. Med Hypotheses 63:574-581.
33. De Santis M, Di Gianantonio E, Straface G, et al. 2005. Ionizing radiation in pregnancy and teratogenesis: a review of literature. Reprod Toxicol 20:323-329.
34. Defoort EN, Kim PM, Winn LM. 2006. Valproic acid increases conservative homologous recombination frequency and reactive oxygen species formation: a potential mechanism for valproic acid-induced neural tube defects. Mol Pharmacol 69:1304-1310.
35. DeSesso JM. 2001. Teratogen update: inorganic arsenic. Teratology 64:170-173.
36. Dinger J, Autenrieth A, Kamin G, et al. 2003. Jejunal atresia related to the use of toluidine blue in genetic amniocentesis in twins. J Perinat Med 31:266-268.
37. Djelic N, Anderson D. 2003. The effect of the antioxidant catalase on oestrogens, triiodothyronine, and noradrenaline in the Comet assay. Teratog Carcinog Mutagen 23:69-81.
38. Donnelly ET, McClure N, Lewis SEM. 1999. The effect of ascorbate and α-tocopherol supplementation in vitro on DNA integrity and hydrogen peroxide-induced DNA damage in human spermatozoa. Mutagenesis 14:505-512.
39. Doyle D, Kapron CM. 2002. Inhibition of cell differentiation by manganese chloride in micromass cultures of mice embryonic limb bud cells. Toxicol In Vitro 16:101-116.
40. Dusek Z, Holejsovská I, Novotná B, Zemanová Z. 2001. Embryotoxicity of 1,2-dibromoethane in chick embryos in ovo: early and late effects. Eur J Morphol 39:105-112.
41. Eder E, Espinosa-Gonzalez J, Mayer A, et al. 2006. Autoxidative activation of the nematocide 1,3-dichloropropene to highly genotoxic and mutagenic derivatives: consideration of genotoxic/carcinogenic mechanisms. Chem Res Toxicol 19:952-959.
42. El-Bassiouni EA, Helmy MH, Rawash NA, El-Zoghby SM. 2005. Embryopathy in experimental diabetic gestation: assessment of oxidative stress and antioxidant defense. Br J Biomed Sci 62:71-76.
43. Enns GM, Roeder E, Chan RT, et al. 1999. Apparent cyclophosphoramide (cytoxan) embryopathy: a distinct phenotype? Am J Med Genet 86:237-241.
44. Eybl V, Kotyzova D, Koutensky J. 2006. Comparative study of natural antioxidants-curcumin, resveratrol and melatonin-in cadmium-induced oxidative damage in mice. Toxicology 225:150-156.
45. Ezendam J, Vissers I, Bleumink R, et al. 2003. Immunomodulatory effects of tetrachlorobenzoquinone, a reactive metabolite of hexachlrobenzene. Chem Res Toxicol 16:688-694.
46. Fantel AG. 1998. Reactive oxygen species in developmental toxicity: review and hypothesis. Teratology 53:196-217.
47. Fernandes PH, Hackfeld LC, Kozekov ID, et al. 2006. Synthesis and mutagenesis of butadiene-derived N3-2′-deoxyuridine adducts. Chem Res Toxicol 19:968-976.
48. Fogu G, Congiu AM, Campus PM, et al. 2000. Genotoxic effects of cadmium chloride on human amniotic fluid cells cultured in vitro. Ann Chim 90:709-714.
49. Foote RH. 1999. Fertility of rabbit sperm exposed in vitro to cadmium and lead. Reprod Toxicol 13:443-449.
50. Foster PM. 2005. Mode of action: impaired fetal Leydig cell function-effects on male reproductive development produced by certain phthalate esters. Crit Rev Toxicol 35:713-719.
51. Frank DA, Augustyn M, Knight WG, et al. 2001. Growth, development, and behavior in early childhood following prenatal cocaine exposure: a systematic review. JAMA 285:1613-1625.
52. Gallagher EP, Sheehy KM. 2001. Effects of phenytoin on glutathione status and oxidative stress biomarker gene mRNA levels in cultured precision human liver slices. Toxicol Sci 59:118-126.
53. Gao L, Li Y, Pei X, Chen X. 2003. Effects of di(2-ethylhexyl)phthalate (DEHP) on mouse embryos development in vitro. Wei Sheng Yan Jiu 32:198-200. [Chinese]
54. Gerber GB, Leonard A, Hantson P. 2002. Carcinogenicity, mutagenicity and teratogenicity of manganese compounds. Crit Rev Oncol Hematol 42:25-34.
55. Godderis L, Aka P, Mateuca R, et al. 2006. Dose-dependent influence of genetic polymorphism on DNA damage induced by styrene oxide, ethylene oxide and gamma-radiation. Toxicology 219:220-229.
56. Gonzalez de Dios J, Moya-Benavent M, Carratala-Marco F. 1999. 'Floppy infant' syndrome in twins secondary to the use of benzodiazepines during pregnancy. Rev Neurol 29:121-123.
57. Goodlett CR, Horn KH, Zhou FC. 2005. Alcohol teratogenesis: mechanisms of damage and strategies for intervention. Soc Exper Biol Med 230:394-406.
58. Gupta U, Cook JC, Tassinari MS, Hurtt ME. 2003. Comparison of developmental toxicology of aspirin (acetylsalicylic acid) in rats using selected dosing paradigms. Birth Defects Res B Dev Reprod Toxicol 68:27-37.
59. Habeebu SS, Liu Y, Park JD, Klaassen CD. 2001. Strain differences in the toxicity of cadmium to trigeminal ganglia in mice. Toxicol Appl Pharmacol 177:200-207.
60. Halliwell B, Gutteridge JMC. 1999. Free radicals in biology and medicine. New York: Oxford University Press. 936 p.
61. Hansen JM, Gong S-G, Philbert M, Harris C. 2002a. Misregulation of gene expression in the redox-sensitive NF-kB-dependent limb outgrowth pathway by thalidomide. Dev Dyn 225:186-194.
62. Hansen JM, Harris KK, Philbert MA, Harris C. 2002b. Thalidomide modulates nuclear redox status and preferentially depletes glutathione in rabbit limb versus rat limb. J Pharmacol Exp Ther 300:768-776.
63. Hansen JM, Harris C. 2004. A novel hypothesis for thalidomide-induced limb teratogenesis: redox misregulation of the NF-kappaB pathway. Antioxid Redox Signal 6:1-14.
64. Hayashi H, Suzuki R, Wakusawa S. 2004. Wilson's disease and its pharmacological treatment. Yakugaku Zasshi 124:711-724. [Japanese]
65. Henderson GI, Chen JJ, Schenker S. 1999. Ethanol, oxidative stress, reactive aldehydes, and the fetus. Front Biosci 4:d541-d550.
66. Hilscherova K, Blankenship AL, Nie M, et al. 2003. Oxidative stress in liver and brain of the hatching chicken (Gallus domesticus) following in ovo injection with TCDD. Toxicol Pharmcol 136:29-45.
67. Hirose A, Takagi A, Nishimura T, et al. 2004. Review of reproductive and developmental toxicity induced by oraganotins in aquatic organisms and experimental animals. National Institute of Health Sciences, Tokyo, Japan. International Symposium on Halogenated Environmental Pollutants and Persistent Organic Pollutants. Organohalogen Compounds 66:3042-3047.
68. Hoffman DJ. 2002. Role of selenium toxicity and oxidative stress in aquatic birds. Aquat Toxicol 57:11-26.
69. Holmes LB, Harvey EA, Coull BA, et al. 2001. The teratogenicity of anticonvulsant drugs. N Engl J Med 344:1132-1138.
70. Homma-Takeda S, Kugenuma Y, Iwamuro T, et al. 2001. Impairment of spermatogenesis in rats by methylmercury: involvement of stage- and cell-specific germ cell apoptosis. Toxicology 169:25-35.
71. Homma-Takeda S, Hiraku Y, Ohkuma Y, et al. 2002. 2,4,6-Trinitrotoluene- induced reproductive toxicity via oxidative DNA damage by its metabolites. Free Radic Res 36:555-566.
72. Hopenhayn-Rich C, Browning SR, Hertz-Picciotto I, et al. 2000. Chronic arsenic exposure and risk of infant mortality in two areas of Chile. Environ Health Perspect 108:667-673.
73. Hovland DN, Machado AF, Scott WJ, Jr, Collins MD. 1999. Differential sensitivity of SWV and C57BL/6 mouse strains to the teratogenic action of single administrations of cadmium given throughout the period of anterior neuropore closure. Teratology 60:13-21.
74. Hu J, Kulkarini AP. 2000. Metabolic fate of chemical mixtures. I. 'Shuttle Oxidant' effect of lipoxygenase-generated radical of chlorpromazine and related phenothiazines on the oxidation of benzidine and other xenobiotics. Teratog Carcinog Mutagen 20:195-208.
75. Hunter ES III. 2000. Role of oxidative damage in arsenic-induced teratogenesis. Teratology 62:240.
76. Iwamuro S, Sakakibara M, Terao M, et al. 2003. Teratogenic and anti-metamorphic effects of bisphenol A on embryonic and larval Xenopus laevis. Gen Comp Endocrinol 133:189-198.
77. Jenkinson PC, Anderson D, Gangolli SD. 2005. Malformations induced in cultured rat embryos by enzymatically generated active oxygen species. Teratog Carcinog Mutagen 6:547-554.
78. Johnson W, Jr. 2002. Final report on the safety assessment of ethoxyethanol and ethoxyethanol acetate. Cosmetic Ingredient Review Expert Panel. Int J Toxicol 21:(Suppl 1):9-62.
79. Karabulut AK, Ulger H, Pratten MK. 2000. Protection by free oxygen radical scavenging enzymes against salicylate-induced embryonic malformations in vitro. Toxicol In Vitro 14:297-307.
80. Kasapinovic S, McCallum GP, Wiley MJ, Wells PG. 2004. The peroxynitrite pathway in development: phenytoin and benzo[a] pyrene embryopathies in inducible nitric oxide synthase knockout mice. Free Radic Biol Med 37:1703-1711.
81. Katayama K, Ishigami N, Suzuki M, et al. 2000a. Teratologic studies on rat perinates and offspring from dams treated with ethylnitrosourea (ENU). Exp Anim 49:181-187.
82. Katayama K, Ishigami N, Uetsuka K, et al. 2000b. Ethylnitrosourea (ENU)-induced apoptosis in the rat fetal tissues. Histol Histopathol 15:707-711.
83. Katayama K, Uetsuka K, Ishigami N, et al. 2001. Apoptotic cell death and cell proliferative activity in the rat fetal central nervous system from dams administered with ethylnitrosourea. Histol Histopathol 16:79-85.
84. Katayama K, Ueno M, Takai H, et al. 2002. Ethylnitrosourea induces apoptosis and growth arrest in the trophoblastic cells of rat placenta. Biol Reprod 67:431-435.
85. Kato F, Ootsuyama A, Nomoto S, et al. 2001. Threshold effect for teratogenic risk of radiation depends on dose-rate and p53-dependent apoptosis. Int J Radiat Biol 77:13-19.
86. Kawai Y, Arinze IJ. 2006. Valproic acid-induced gene expression through production of reactive oxygen species. Cancer Res 66:6563-6569.
87. Kaya B. 2003. Anti-genotoxic effect of ascorbic acid on mutagenic dose of three alkylating agents. Turk J Biol 27:241-246.
88. Kazy Z, Puhó E, Czeizel AE. 2005. Teratogenic potential of vaginal metronidazole treatment during pregnancy. Eur J Obstet Gynecol Reprod Biol 123:174-178.
89. Kennedy JC, Memet S, Wells PG. 2004. Antisense evidence for nuclear factor-kB-dependent embryopathies initiated by phenytoin-enhanced oxidative stress. Mol Pharmacol 66:404-412.
90. Knight AP, Walter RG. 2004. Plants associated with congenital defects and reproductive failure. In: Knight AP, Walter RG, editors. A guide to plant poisoning of animals in North America. Jackson, WY: Teton New Media. pp. 270-291.
91. Koizumi M, Ema M, Hirose A, Hasegawa R. 2000. Recent studies on toxic effects of phthalate esters on reproduction and development: focus on di(2-ethylhexyl) phthalate and di-n-butyl phthalate. Nippon Shokuhin Kagaku Gakkaishi. J Food Sci Technol (Japan) 7:65-73. [Japanese]
92. Kokilavani V, Devi MA, Sivarajan K, Panneerselvam C. 2005. Combined efficacies of DL-alpha-lipoic acid and meso 2,3 dimercaptosuccinic acid against arsenic induced toxicity in antioxidant systems of rats. Toxicol Lett 160:1-7.
93. Kovacic P, Edwards DW, Natale NR, et al. 1990a. Theoretical calculations on calcium channel drugs: is electron transfer involved mechanistically? Chem Biol Interact 75:61-70.
94. Kovacic P, Kiser PF, Feinberg BA. 1990b. Are reduction potentials of antifungal agents relevant to activity? Pharm Res 7:283-288.
95. Kovacic P, Becvar LE. 2000. Mode of action of anti-infective agents: emphasis on oxidative stress and electron transfer. Curr Pharm Des 6:143-167.
96. Kovacic P, Osuna JA. 2000. Mechanisms of anticancer agents: emphasis on oxidative stress and electron transfer. Curr Pharm Des 6:277-309.
97. Kovacic P, Jacintho JD. 2001a. Mechanisms of carcinogenesis: focus on oxidative stress and electron transfer. Curr Med Chem 8:773-796.
98. Kovacic P, Jacintho JD. 2001b. Reproductive toxins: pervasive theme of oxidative stress and electron transfer. Curr Med Chem 8:863-892.
99. Kovacic P, Sacman A, Wu-Weis M. 2002. Nephrotoxins: widespread role of oxidative stress and electron transfer. Curr Med Chem 9:823-847.
100. Kovacic P. 2005. Role of oxidative metabolites of cocaine in toxicity and addiction: oxidative stress and electron transfer. Med Hypotheses 64:350-356.
101. Kovacic P, Cooksy AL. 2005. Unifying mechanism for toxicity and addiction by abused drugs: electron transfer and reactive oxygen species. Med Hypotheses 64:367-366.
102. Kovacic P, Thurn LA. 2005. Cardiovascular toxins from the perspective of oxidative stress and electron transfer. Curr Vasc Pharmacol 3:107-117.
103. Kovacic P, Somanathan R. 2005. Neurotoxicity: The broad framework of electron transfer, oxidative stress and protection by antioxidants. Curr Med Chem-CNS Agents 5:249-258.
104. Kovacic P, Pozos RS, Somanathan R, et al. 2005. Mechanism of mitochondrial uncouplers, inhibitors, and toxins: focus on electron transfer, free radicals, and structure-activity relationships. Curr Med Chem 5:2601-2623.
105. Kovacic P. 2006. Novel electrochemical approach to enhanced toxicity of 4-oxo-2-nonenal vs. 4-hydroxy-2-nonenal (role of imine): oxidative stress and therapeutic modalities. Med Hypotheses 67:151-156.
106. Kovacic P, Somanathan R. 2006. Beneficial effects of antioxidants in relation to carcinogens, toxins and various illnesses. In: Panglossi HV, editor. Frontiers in antioxidants research. Hauppauge, NY: Nova Science Publishers: pp. 49-101.
107. Kovacic P, Pozos RS. Cell signaling (mechanism and reproductive toxicity): redox chains, messengers (radicals and precursors, electrons), relays, conduits, electrochemistry, and medical implications. Birth Defects Research (in press).
108. Kumar P, Prasad AK, Saxena DK, et al. 2000. Fertility and general reproduction studies in trichloroethylene exposed rats. Ind J Occup Health 43:117-126.
109. Kumar S, Sathwara NG, Gautam AK, et al. 2005. Semen quality of industrial workers occupationally exposed to chromium. J Occup Health 47:424-430.
110. Lavolpe M, Greco LL, Kesselman D, Rodriguez E. 2004. Differential toxicity of copper, zinc, and lead during the embryonic development of Chasmagnathus granulatus (Brachura, Varunidae). Environ Toxicol Chem 23:960-967.
111. Lee KM, Muralidhara S, White CA, Bruckner JV. 2000. Mechanisms of the dose-dependent kinetics of trichloroethylene: oral bolus dosing of rats. Toxicol Appl Pharmacol 164:55-64.
112. Lee J, Park J, Jang B, Knudsen TB. 2004. Altered expression of genes related to zinc homeostasis in early mouse embryos exposed to di-2-ethylhexyl phthalate. Toxicol Lett 152:1-10.
113. Lee SK, Owens GA, Veeramachaneni DN. 2005. Exposure to low concentrations of di-n-butyl phthalate during embryogenesis reduces survivability and impairs development of Xenopus laevis frogs. J Toxicol Environ Health A 68:763-772.
114. Léonard A, Gerber GB, Stecca C, et al. 1999. Mutagenicity, carcinogenicity, and teratogenicity of acrylonitrile. Mut Res 436:263-283.
115. Li H, Chen Q, Li S, Xu Y, Yao W, Chen C. 1999. Studies on male reproductive toxicity caused by hexavalent chromium. Zhonghua Yu Fang Yi Xue Za Zhi 33:351-353. [Chinese]
116. Li Y, Pei X, Long D, Chen X. 2003. Teratogenicity of bisphenol A on post-implanted rat and mouse embryos: an in vitro study. Wei Sheng Yan Jiu 32:89-92. [Chinese]
117. Liang R, Senturker S, Shi X, et al. 1999. Effects of Ni(II) and Cu(II) on DNA interaction with the N-terminal sequence of human protamine P2: enhancement of binding and mediation of oxidative DNA strand scission and base damage. Carcinogenesis 20:893-898.
118. Liao VH, Yu CW. 2005. Caenorhabditis elegans gcs-1 confers resistance to arsenic-induced oxidative stress. Biometals 18:519-528.
119. Lin D, Lee H-G, Liu Q, et al. 2005. 4-Oxi-2-nonenal is both neurotoxic and more protein reactive than 4-hydroxy-2-nonenal. Chem Res Toxicol 18:1219-1231.
120. 6-alkylguanine DNA alkyl-transferase to DNA in the presence of 1,2,3,4-diepoxybutane. Chem Res Toxicol 19:645-654.
121. Lovekamp-Swant T, Davis BJ. 2003. Mechanisms of phthalate ester toxicity in the female reproductive system. Environ Health Perspect 111:139-145.
122. Manini P, De Palma , Andreoli R, et al. 2003. Urinary excretion of 4-vinylphenol after experimental and occupational exposure to styrene. G Ital Med Lav Ergon 25:S61-S62.
123. Markey CM, Michaelson CL, Sonnenschein C, Soto AM, Metzler M, eds. 2001. Alkylphenols and bisphenol A as environmental estrogens. The handbook of environmental chemistry. Berlin: Springer. pp. 129-153.
124. Maroni M, Colosio C, Ferioli A, Fait A. 2000. Biological monitoring of pesticide exposure; a review. Introduction. Toxicology 143:1-118.
125. Matta MB, Linse J, Cairncross C, et al. 2001. Reproductive and transgenerational effects of methylmercury or Aroclor 1268 on Fundulus heteroclitus. Environ Toxicol Chem 20:327-335.
126. Mittendorf R. 1995. Teratogen update: carcinogenesis and teratogenesis associated with exposure to diethylstilbestrol (DES) in utero. Teratology 51:435-445.
127. Moran LK, Gutteridge JMC, Quinlan GJ. 2001. Thiols in cellular redox signaling and control. Curr Med Chem 8:763-772.
128. Murata M, Bansho Y, Inoue S, et al. 2001. Requirement of glutathione and cysteine in guanine-specific oxidation of DNA by carcinogenic potassium bromate. Chem Res Toxicol 24:678-685.
129. Mussali-Galante P, Rodriguez-Lara V, Hernandez-Tellez, et al. 2005. Inhaled vanadium pentoxide decreases gamma-tubulin of mouse testes at different exposure times. Toxicol Ind Health 21:215-222.
130. Nagao T, Saitoh Y, Yoshimura S. 2000. Possible mechanism of congenital malformations induced by exposure of mouse preimplantation embryos to mitomycin C. Teratology 61:248-261.
131. Náprstková I, Radochová B, Novotná B, et al. 2005. Quantitative analysis of embryonic kidney impairment by confocal microscopy and sterology; effect of 1,2-dibromoethane in the chick mesonephros. Br Poult Sci 46:661-667.
132. Nardiello S, Pizzella T, Ariviello R. 2002. Risks of antibacterial agents in pregnancy. Infez Med 10:8-15.
133. Ognio E, Lapide M, Ottone M, et al. 2003. Embryo-lethal and teratogenic effect of the new platinum compound DPR in pregnant mice. Arch Toxicol 77:584-590.
134. Ohkuma Y, Kawanishi S. 1999. Oxidative DNA damage by a metabolite of carcinogenic and reproductive toxic nitrobenzene in the presence of NADH and Cu(II). Biochem Biophys Res Commun 257:555-560.
135. Padmanabhan R, Abdulrazzaq SMA, Baskati SMA, et al. 2003. Experimental studies on reproductive toxicologic effects of lamotrigine in mice. Birth Defects Res B Dev Reprod Toxicol 68:428-438.
136. Pagano G, De Biase A, Deeva IB, et al. 2001. The role of oxidative stress in developmental and reproductive toxicity of tamoxifen. Life Sci 68:1735-1749.
137. Palmieri C, Canger R. 2002. Teratogenic potential of the newer antiepileptic drugs: what is known and how should this influence prescribing?. CNS Drugs 16:755-764.
138. Park JH, Troxel AB, Harvey RG, Penning TM. 2006. Polycyclic aromatic hydrocarbon (PAH) o-quinones produced by the aldo-keto- reductases (AKRs) generate abasic sites, oxidized pyrimidines, and 8-oxo-d-Guo via reactive oxygen species. Chem Res Toxicol 19:719-728.
139. Parman T, Chen G, Wells PG. 1998. Free radical intermediates of phenytoin and related teratogens. J Biol Chem 273:25079-25088.
140. Parman T, Wells PG. 2002. Embryonic prostaglandin H synthase-2(PHS-2) expression and benzo[a]pyrene teratogenicity in PHS-2 knockout mice. FASEB J 16:1001-1009.
141. Perez-Paten R, Martinez-Galero E, Garduno-Siciliano L, et al. 2006. Effects of dimethylsulfoxide on mice arsenite-induced dysmorphogenesis in embryo culture and cytotoxicity in embryo cells. Toxicol Lett 161:167-173.
142. Pinkofsky HB. 2000. Effects of antipsychotics on the unborn child: what and how should this influence prescribing? Paediatr Drugs 2:83-90.
143. Pocar P, Nestler D, Risch M, Fischer B. 2005. Apoptosis in bovine cumulus-oocyte complexes after exposure to polychlorinated biphenyl mixtures during in vitro maturation. Reproduction 130:857-868.
144. Poli G, Cheesman KH, Dianzani MU, Slater TF. 1989. Free radicals in the pathogenesis of liver injury. New York: Pergamon. pp. 1-330.
145. Prater MR, Zimmerman KL, Pinn LC, et al. 2006. Role of maternal dietary antioxidant supplementation in murine placental and fetal limb development. Placenta 27:502-509.
146. Purohit V, Basu AK. 2000. Mutagenicity of nitroaromatic compounds. Chem Res Toxicol 13:673-686.
147. Rao MV, Sharma PS. 2001. Protective effect of vitamin E against mercuric chloride reproductive toxicity in male mice. Reprod Toxicol 15:705-712.
148. Rouveix B, Levacher M, Giroud JP. 1999. Drugs for respiratory tropism and pregnancy. Rev Pneumol Clin 55:338-343.
149. Saillenfait AM, Sabatéte JP, Gallissot F. 2006. Developmental toxic effects of diisobutyl phthalate, the methyl-branched analogue of di-n-butyl phthalate, administered by gavage to rats. Toxicol Lett 165:39-46.
150. Sallmen M. 2001. Exposure to lead and male fertility. Int J Occup Med Environ Health 14:219-222.
151. Salvatori F, Talassi CB, Salzgeber SA, et al. 2004. Embryotoxic and long-term effects of cadmium exposure during embryogenesis in rats. Neurotoxicol Teratol 26:673-680.
152. Samikkannu T, Chen C-H, Yih L-H, et al. 2003. Reactive oxygen species are involved in arsenic trioxide inhibition of pyruvate dehydrogenase activity. Chem Res Toxicol 16:409-414.
153. Saradha B, Mathur PP. 2006. Effect of environmental contaminants on male reproduction. Toxicol Pharmacol 21:34-41.
154. Satoh H. 2003. Behavioral teratology of mercury and its compounds. Tohoku J Exp Med 201:1-9.
155. Sauer H, Günther J, Hescheler J, Wartenberg M. 2000. Thalidomide inhibits angiogenesis in embryoid bodies by the generation of hydroxyl radicals. Am J Pathol 156:151-158.
156. Schettler T, Solomon G, Valenti M, Huddle A. 1999. Generations at risk: reproductive health and the environment. Cambridge, MA: MIT Press. 417 p.
157. Shea KM. 2003. Pediatric exposure and potential toxicity of phthalate plasticizers. Pediatrics 111:1467-1474.
158. Shi H, Hudson LG, Ding W, et al. 2004. Arsenite causes DNA damage in keratinocytes via generation of hydroxyl radicals. Chem Res Toxicol 17:871-878.
159. Sikka SC. 2001. Relative impact of oxidative stress on male reproductive function. Curr Med Chem 8:851-862.
160. Sikka SC. 2003. Role of oxidative stress response elements and antioxidants in prostrate cancer pathology and chemoprotection. Curr Med Chem 10:2679-2692.
161. Simmons DB, Wallschlager D. 2005. A critical review of the biogeochemistry and ecotoxicology of selenium in lotic and lentic environments. Environ Toxicol Chem 24:1331-1343.
162. Sinha S, Taly AB, Prashanth LK, et al. 2004. Successful pregnancies and abortions in symptomatic and asymptomatic Wilson's disease. J Neurol Sci 217:37-40.
163. Soto-Reyes E, del Razo LM, Valverde M, Rojas E. 2005. Role of the alkali labile sites, reactive oxygen species and antioxidants in DNA damage induced by methylated trivalent metabolites of inorganic arsenic. Biometals 18:493-506.
164. Spiegelstein O, Chatterjie N, Alexander G, Finnell RH. 2003. Teratogenicity of valproate conjugates with anticonvulsant activity in mice. Epilepsy Res 57:145-152.
165. Subramanian S, Rajendiran G, Sekhar P, et al. 2006. Reproductive toxicity of chromium in adult bonnet monkeys (Macaca radiate Geoffrey). Reversible oxidative stress in the semen. Toxicol Appl Pharmacol.
166. Sugihara K, Kitamura S, Yamada T, et al. 2001. Aryl hydrocarbon receptor (AhR)-mediated induction of xanthine oxidase/xanthine dehydrogenase activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Biochem Biophys Res Commun 281:1093-1099.
167. Tang W, Abbott FS. 1996a. Characterization of thiol-conjugated metabolites of 2-propylpent-4-enoic acid (4-ene VPA), a toxic metabolite of valproic acid, by electrospray tandem mass spectrometry. J Mass Spectrom 31:926-936.
168. Tang W, Abbott FS. 1996b. Bioactivation of a toxic metabolite of valproic acid, (E)-2-propyl-2,4-pentadienoic acid, via glucuronidation. LC/MS/MS characterization of the GSH-glucuronide diconjugates. Chem Res Toxicol 9:517-526.
169. Tang W, Borel AG, Abbott FS. 1996. Conjugation of glutathione with toxic metabolite of valproic acid, (E)-2-propyl-2,4-pentadienoic acid, catalyzed by rat hepatic glutathione-S-transferases. Drug Metab Dispos 24:436-446.
170. Tapner MJ, Jones BE, Wu WM, Farrel GC. 2004 Toxicity of low dose azathioprine and 6-mercaptopurine in rat hepatocytes. Role of xanthine oxidase and mitochondrial injury. J Hepatol 40:454-463.
171. Tchounwou PB, Ayensu WK, Ninashvili N, Sutton D. 2003. Environmental exposure to mercury and its toxicopathologic implications for public health. Environ Toxicol 18:149-175.
172. Teh SJ, Deng X, Teh FC, Hung SO. 2002. Selenium-induced teratogenicity in Sacramento splittail (Pogonichthys macrolepidotus). Mar Environ Res 54:605-608.
173. Thomas RD, Roy D. 1995. Mitochondrial enzyme-catalyzed oxidation and reduction reactions of stilbene estrogen. Carcinogenesis 16:891-895.
174. Thompson J, Bannigan J. 2001. Effects of cadmium on formation of the ventral body wall in chick embryos and their prevention by zinc pretreatment. Teratology 64:87-97.
175. Thrasher JD, Kilburn KH. 2001. Embryo toxicity and teratogenicity of formaldehyde. Arch Environ Health 56:300-311.
176. Tiboni GM, Lamonaca D. 2001. Transplacental exposure to methylene blue initiates teratogenesis in the mouse; preliminary evidence for a mechanistic implication of cyclic GMP pathway disruption. Teratology 64:213-220.
177. Tong V, Teng XW, Chang TK, Abbott FS. 2005. Valproic acid I: time course of lipid peroxidation biomarkers, liver toxicity, and valproic acid metabolite levels in rats. Toxicol Sci 86:427-435.
178. Toraason M, Clark J, Dankovic D, et al. 1999. Oxidative stress and DNA damage in Fischer rats following acute exposure to trichloroethylene and perchloroethylene. Toxicology 138:43-53.
179. Usami M, Tabata H, Ohno Y. 1999. Effects of ascorbic acid on selenium teratogenicity in cultured rat embryos. Toxicol Lett 29:123-128.
180. Vaux KK, Kahole NC, Jones KL. 2003. Cyclophosphamide, methotextrate, and cytarabine embryopathy: is apoptosis the common pathway?. Birth Defects Res A Clin Mol Teratol 67:403-408.
181. 2 induces abnormal tail flexure in Xenopus embryos: similarities with paraquat teratogenic effects. Birth Defects Res B Dev Reprod Toxicol 77:238-243.
182. Vitseva O, Flochart DA, Jin Y, et al. 2005. The effects of tamoxifen and its metabolites on platelet function and release of reactive oxygen intermediates. J Pharmacol Exp Ther 312:1144-1150.
183. Wadi SA, Ahmad G. 1999. Effects of lead on the male reproductive system in mice. J Toxicol Environ Health A 56:513-521.
184. Wang B. 2001. Involvement of p53-dependent apoptosis in radiation teratogenesis and in the radioadaptive response in the late organogenesis of mice. J Radiat Res (Tokyo) 42:1-10.
185. Wang L, Jia G. 2005. Progress in developmental toxicity of methylmercury. Wei Sheng Yan Jiu 34:633-635. [Chinese]
186. Wells PG, Bhuller Y, Chen CS, et al. 2005. Molecular and biochemical mechanisms in teratogenesis involving reactive oxygen species. Toxicol Appl Pharmacol 207:354-366.
187. Winn LM, Wells PG. 1999. Maternal administration of superoxide dismutase and catalase in phenytoin teratogenicity. Free Radic Biol Med 26:266-274.
188. Winn LM, Wells PG. 2002. Evidence for Ras-dependent signal transduction in phenytoin teratogenicity. Toxicol Appl Pharmacol 184:144-152.
189. Wlodarczyk BJ, Cabrera RM, Hill DS, et al. 2006. Arsenic-induced gene expression changes in the neural tube of folate transport defective mouse embryos. Neurotoxicology 27:547-557.
190. Woo GH, Katayama K, Jung JY, et al. 2003. Hydroxyurea (HU-induced apoptosis in the mouse fetal tissues. Histol Histopathol 18:387-392.
191. Woo GH, Katayama K, Bak EJ, et al. 2004. Effects of prenatal hydroxyurea-treatment on mouse offspring. Exp Toxicol Pathol 56:1-7.
192. Woo GH, Bak EJ, Nakayama H, Doi K. 2005. Molecular mechanisms of hydroxyurea (HU)-induced apoptosis in the mouse. Neurotoxicol Teratol 28:125-134.
193. Xu Y, Cook TJ, Knipp GT. 2005. Effects of di-(2-ethylhexyl)-phthalate (DEHP) and its metabolites on fatty acid homeostasis regulating proteins in rat placental HRP-1 trophoblast cells. Toxicol Sci 84:287-300.
194. Yamanaka H. 1998. Protective effects of α-tocopherol against fetal abnormalities developing in a hyperglycemic environment. Kurume Igakkai Zasshi. Toxicol Sci 61:271-278. [Japanese]
195. Yan J, Hales BF. 2005. Activator protin-1 (AP-1) DNA binding activity is induced by hydroxyurea in organogenesis stage mouse embryos. Teratol Sci 85:1013-1023.
196. Yang P-H, Gao H-Y, Cai J, et al. 2005. The stepwise process of chromium-induced DNA breakage: characterization by electrochemistry, atomic force microscopy, and DNA electrophoresis. Chem Res Toxicol 18:1563-1566.
197. Yousef MI, El-Morsy AMA, Hassan MS. 2005. Aluminum-induced deterioration in reproductive performance and seminal plasma biochemistry of male rabbits: protective role of ascorbic acid. Toxicology 215:97-107.
198. Yu RC-T, Lee T-C, Wang TC, Li J-H. 1999. Genetic toxicity of cocaine. Carcinogenesis 20:1193-1199.
199. Zadrozana M. 2003. Recent environmental toxic effect in the Polish copper mining territory on human reproduction. Part I. Response of the placenta to the chemical stress. Folia Biol (Krakow, Poland) 51:201-205.
200. Zaken V, Kohen R, Ornoy A. 2000. The development of antioxidant defense mechanism in young rat embryos in vivo and in vitro. In: Barnea ER, editor. Early pregnancy. Biology and medicine, Vol. IV, pp. 110-123.
201. Zhao S, Narang A, Ding X, Eadon G. 2004. Characterization and quantitative analysis of DNA adducts formed from lower chlorinated PCB-derived quinones. Chem Res Toxicol 17:502-511.
202. Zhao Z, Kosinska W, Khmelnitsky M, et al. 2006. Mutagenic activity of 4-hydroxyestradiol, but not 2-hydroxyestradiol, in BB rat2 embryonic cells, and the mutational spectrum of 4-hydroxyestradiol. Chem Res Toxicol 19:475-479.
203. Zhitkovich A. 2005. Importance of chromium-DNA adducts in mutagenicity and toxicity of chromium (VI). Chem Res Toxicol 18:3.