Role of dehydroepiandrosterone in experimental and human carcinogenesis

Dehydroepiandrosterone (DHEA): Biochemical, Physiological and Clinical Aspects

Volumn , Issue , 2011, Pages 215-236

  Feo, Francesco ^a   Pascale, Rosa M ^a   Simile, Maria M ^a   De Miglio, Maria R ^a  

^a Division of Experimental Pathology and Oncology   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85064921891     PISSN: None     EISSN: None     Source Type: Book    
DOI: None     Document Type: Chapter

References (138)

1. Araghiniknam, M, Chiung, S., Nelson-White, T, Eskelson, C., and Watson, R. R. (1996). Antioxidant activity of dioscorea and dehydroepiandrosterone (DHEA) in older humans. Lise Sei. 59, 147-157
2. Aragno, M., Brignardello, E., Tamagno, E., Gatto, V., Danni, O., and Boccuzzi, G. (1997). Dehydroepiandrosterone administration prevents the oxidative damage induced by actute hyperglycemia in rats. J. Endocrinol. 155, 233-240
3. Aragno, M, Tamagno, E, Poli, G., Boccuzzi, G., Brignardello, E., and Danni, O. (1994). Prevention of carbon tetrachloride-induced lipid peroxidation in liver microsomes from dehydroepiandrosterone-pretreated rats. Free Rad. Res. 21, 427-435
4. Bannasch, P., D'Introno, A., Leonetti, P., Metzger, C, Klimek, E, and Mayer, D. (1998). Early abberations of energy metabolism in carcinogenesis. In: Cell Growth and Oncogenesis, P. Bannasch, D. Kanduc, S. Papa, and J. M.Tager, eds. (Birkhäuser Verlag, Basel), pp. 191-212
5. Barrett-Connor, E., Friedlander, N. J., and Khaw, K. T. (1990). Dehydroepiandrosterone sulfate and breast cancer risk. Cancer Res. 50, 6571-6574
6. Battino, M., Fato, R., Parenti-Castelli, G., and Lenaz, G. (1990). Coenzyme Q can control the efficiency of oxidative phosphorylation. Int. J. Tissue React. 12, 137-144
7. Beck, L. A., Khosick, I. J., and Sinisky, M. (1988). Incorporation of product of mevalonic acid metabolism in proteins of Chinese hamster ovary cell nuclei. J. Cell Biol. 197, 1307-1313
8. Beier, K., Völkl, A., Metzger, C, Mayer, D, Bannasch, P., and Fahimi, H. D. (1997). Hepatic zonation of the induction of cytochrome P450 IVA, peroxisomal lipid β-oxidation enzymes and peroxisome proliferation in and sex-specific differences. Carcinogenesis 18, 1491-1498
9. Bernstein, L., Ross, R. K., Pike, M. C., Brown, J. B., and Henderson, B. E. (1990). Hormone levels in older women: study of post-menopausal breast cancer patients and healthy population controls. Br. J. Cancer 61, 298-302
10. Boccuzzi, G., Aragno, M., Seccia, M., Brignardello, E., Tamagno, E., Albano, E., Danni, O., and Bellomo, G. (1997). Protective effect of dehydroepiandrosterone against cupper-induced lipid peroxidation in the rat. Free Rad. Biol. Med. 22, 1289-1294
11. Boccuzzi, G, Brignardello, E., Di Monaco, M, Forte, C., Leonardi, L., and Pizzini, A. (1992). Influence of dehydroepiandrosterone and 5-en-androstene-3-beta, 17beta-diol on the growth of MCF-7 human breast cancer cells induced by 17beta-estradiol. Anticancer Res. 12, 799-803
12. Boccuzzi, G., Di Monaco, M., Brignardello, E., Leonardi, L., Gatto, V., Pizzini, O., and Gallo, M. (1993). Dehydroepiandrosterone antiestrogenic action through androgen receptor in MCF-7 human breast cancer cell line. Anticancer Res. 13, 2267-2272
13. Boone, C. W. and Kelloff, G. J. (1997). Biomarker end-points in cancer chemoprevention trials. IARC Scientific Publ. 142, 273-280
14. Brennan, N. J., Wang, D. Y, Hayward, J. L., Bulbrook, R. D., and Deshpande, N. (1973). Urinary and plasma androgens in benign breast disease. Possible relation to breast cancer. Lancet 1, 1076-1079
15. Browsey, B, Cameron, E. H. D., Griffiths, K, Glewave, E. N, Forest, A. P. M, and Campbel, H. (1972). Plasma dehydroepiandrosterone sulfate levels in patients with benign and malignant breast disease. Eur. J. Cancers, 131-137
16. Bulbrook, R. D., Hayward, J. L., Spicer, C. C., and Thomas, B. S. (1962). Abnormal excretion of urinary steroids by women with early breast cancer. Lancet 2, 1238-1240
17. Casazza, J. P., Schaffer, W. T., and Veech, R. L. (1986). The effect of dehydroepiandrosterone on liver metabolites. J. Nutr. 116, 304-310
18. Chojnaki, T. and Daliner, G. (1988). Biological role of dolichol. J. Biochem. 251, 1-9
19. Cleary, M. P., Hood, S. S, Chando, C., Hansen, C. T, and Billheimer, J. T. (1984). Response of sucrose-fed BHE rats to dehydroepiandrosterone. Nutr. Res. 4, 485-494
20. Dorgan, J. F., Stanczyk, F. Z, Longcope, C., Stefenson, H. E, Chang, L, Miller, R., Franz, C., Falk, R. T., and Kahle, L. (1997). Relationship of serum dehydroepiandrosterone (DHEA) DHEA sulfate, and 5-androstene-3 β, 17 β-diol to risk of breast cancer in postmenopausal women. Cancer Epidem. Biomarker Prev. 6, 177-181
21. Dvorkin, C. R, Gorman, S. D, Pashko, L. L, Cristofalo, V. J., and Schwartz, A. G. (1986). Inhibition of growth of HeLa and WI-38 cells by dehydroepiandrosterone and its reversal by ribo-and deoxyribo-nucleosides. Life Sei. 38, 1451-1457
22. Eckl, P. and Esterbauer, H. (1989). Genotoxic effects of 4-hydroxyalkenals. In: Free Radicals in the Pathogenesis of Liver Injury, G. Poli, K. H. Cheeseman, M. U. Dianzani, andT. F. Slater, eds. (Pergamon Press, Oxford), pp. 141-157
23. Enomoto, K. and Farber, H. (1982). Kinetics of phenotypic maturation of emodeling hyperplastic nodules during liver carcinogenesis. Cancer Res. 42, 2330-2335
24. Feo, F. and Pascale, R. (1990). Glucose-6-phosphate dehydrogenase and the relation of dehydroepiandrosterone to carcinogenesis. In: The Biologic Role of Dehydroepiandrosterone (DHEA), M. Kalimi and W. Regelson, eds. (Walter de Gruyter, Berlin), pp. 331-360
25. Feo, F., Daino, L, Seddaiu, M. A., Simile, M. M, Pascale, R. M, McKeating, J. A., Davliakos, G. P., Sudol, K. S., Melhem, M. F., and Rao, K. N. (1991). Differential effects of dehydroepiandrosterone and deoxyribonucleosides on DNA synthesis and de novo cholesterogenesis in hepatocarcinogenesis in rat. Carcinogenesis 12, 1581-1586
26. Frenkel, R. A., Slaughter, C. A., Orth, K., Momaw, C. R, Hicks, S. H, Snyder, K. J. M, Bennet, M, Prough, R. A., Putnam, R. S., and Milewich, L. (1990). Peroxisome proliferation and induction of peroxisomal enzymes in mouse and rat liver by dehydroepiandrosterone feeding. J. Steroid Biochem. 35, 333-342
27. Garcea, R., Daino, L., Frassetto, S., Cozzolino, P., Ruggiu, M. E., Vannini, M. G., Pascale, R. M., Lenzerini, L., Simile, M. M., Puddu, M., and Feo, F. (1988). Reversal by ribo-and deoxyribonucleosides of dehydroepiandrosterone-induced inhibition of enzyme altered foci in the liver of rats subjected to the initiation-selection process of experimental carcinogenesis. Carcinogenesis 9, 931-938
28. Garcea, R., Daino, L., Pascale, R. M., Frassetto, S., Cozzolino, P., Ruggiu, M. E., and Feo, F. (1987). Inhibition by dehydroepiandrosterone of liver preneoplastic foci formation in rats after initiation-selection in experimental carcinogenesis. Toxicol. Pathol. 15, 164-168
29. Garcea, R, Daino, L, Pascale, R. M, Simile, M. M., Puddu, M, Ruggiu, M. E, Seddaiu, M. A., Satta, G, Sequenza, M. J., and Feo, F. (1989). Protooncogene methylation and expression in regenerating and preneoplastic liver nodules induced in the rat by diethylnitrosamine: Effect of variations of S-adenosyl-Lmethionine: S-adenosyl-homocysteine ratio. Carcinogenesis 10, 1183-1192
30. Gerbracht, U., Eigenbrodt, E., Simile, M. M., Pascale, R. M., Gaspa, L., Daino, L., Seddaiu, M. A., De Miglio, M. R., Nufris, A., and Feo, F. (1993). Effect of S-adenosyl-L-methionine on the development of preneoplastic foci and the activity of some carbohydrate metabolizing enzymes in the liver, during experimental hepatocarcinogenesis. Anticancer Res. 13, 1965-1972
31. Gianelly, A. A. and Terner, C. (1968). Inhibition of cholesterol biosynthesis by dehydroepiandrosterone in lactating mammary gland. Endocrinology 83, 1311-1315
32. Gldfarb, A. H., Mcintosh, M. K., Boyer, B. T., and Fatouros, J. (1994). Vitamin E effects on indexes of lipid peroxidation in muscle from DHEA-treated and exercised rats. J. Appl. Physiol. 76, 1630-1635
33. Goldstein, J. L. and Brown, M. S. (1984). Progress in understanding the LDL receptor and HMG-CoA reductase, two membrane proteins that regulate the plasma cholesterol. J. Lipid. Res. 25, 1450-1461
34. Gomes, P., Cassanas, G., Halberg, F., Hermida, R, Röbel, P., Baulieu, E. E., Lakatua, D., and Hans, E. (1988). Taux sanguin de sulfate de la dehydroepiandrosterone (DHEA-S) et risque de cancer du sein. C. R. Acad. Sei. Paris 306, 261-264
35. Gordon, G. B, Bush, T. L, Helzlsouer, K. J., Miller, S. R., and Comstock, G. W. (1990). Relationship of serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate to the risk of developing postmenopausal breast cancer. Cancer Res. 50, 3859-3862
36. Gordon, G. B., Shantz, L. M., and Talalay, P. (1987). Modulation of growth, differentiation and carcinogenesis by dehydroepiandrosterone. Adv. Enzyme Regul. 26, 355-382
37. Göttlicher, M., Widmark, E., Li, Q., and Gustafsson, J. A. (1992). Fatty acids activate a chimera of the clofibric acid-activated receptor and the glucocorticoid receptor. Proc. Natl. Acad. Sei. USA 89, 4653-4657
38. Hackenberg, R., Turgetto, I., Filmer, A., and Schulz, K. (1993). Estrogen and androgen receptor mediated stimulation and inhibition of proliferation by androsten-5-ene-3β, 17β-diol in human mammary cancer cells. J. Steroid Biochem. Molec. Biol. 46, 597-603
39. Hamilton, S. R., Gordon, G. B., Floyd, J., and Golightly, S. (1991). Evaluation of dietary dehydroepiandrosterone for chemoprevention against tumorigenesis in premalignant colonic epithelium of male F344 rats. Cancer Res. 57, 476-480
40. Hanckock, J. F., Magee, A. I., Childs, J. E., and Marshyall, C. Y. (1989). All ras proteins are polyisoprenylated but only some are palmitoylated. Cell 57, 1167-1177
41. Hayashi, F., Tamura, H., Yamada, J., Kasai, H., and Suga, T. (1994). Characteristics of the hepatocarcinogenesis caused by dehydroepiandrosterone, a peroxisome proliferator in male F-344 rats. Carcinogenesis 15, 2215-2219
42. Helzlsouer, K. J., Alberg, A. J., Gordon, G. B., Longcope, C., Bush, T. L., Hoffman, S. C., and Comstock, G. W. (1995). Serum gonadotropins and steroid hormones and the development of ovarian cancer. J. A.M. A. 274, 1926-1930
43. Helzlsouer, K. J., Gordon, G. B., Alberg, A. J., Bush, T. L., and Comstock, G. W. (1992). Relationship of prediagnostic serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate to the risk of developing premenopausal breast cancer. Cancer Res. 52, 1-4
44. Hilgertova, J. and Sonka, J. (1973). Effects of cold exposure, thyroid extract, methylthiouracil and dehydroepiandrosterone on glucose-6-phosphate and 6-phosphogluconate dehydrogenases in rat liver and erythrocytes. Horm. Metab. Res. 5, 286-289
45. Hobe, G., Hillesheim, H. G., Schön, R, Reddersen, G., Knappe, R, Bannasch, P., and Mayer, D. (1994). Sex differences in dehydroepiandrosterone metabolism in the rat: different plasma levels following ingestion of DHEA-s supplemented diet and different metabolite patterns in plasma, bile and urine. Horm. Metab. Res. 26, 326-329
46. Issemann, I. and Green, S. (1990). Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347, 6465-650
47. Khalil, A., Lehoux, J.-G., Wagner, R. J., Lesur, O., Cruz, S., Dupont, E., Jay-Guerin, J.-P., Wallach, J., and Fiilöp, T. (1998). Dehydroepiandrosterone protects low density lipoproteins against peroxidation by free radicals produced by γ-radiolysis of ethanol-water mixtures. Atherosclerosis 136, 99-107
48. Kimura, S, Harwick, J. P., Kozak, C. A., and Gonzalez, F. J. (1989). The rat Clofibrate inducible CYP4A subfamily. II. cDNA sequence of IVA3, mapping of the Cyp4A locus to mouse chromosome 4, and coordinate and tissue-specific regulation of the CYP4A genes. DNA 8, 517-525
49. Knudsen, T. T. and Mahesh, V. B. (1975). Initiation of precocious sexual maturation in the immature rat treated with dehydroepiandrosterone. Endocrinology 97, 458-468
50. Lam, L. K. and Zhang, J. (1991). Reduction of aberrant crypt formation in the colon of CF1 mice by potential chemopreventive agents. Carcinogenesis 12, 2311-2315
51. Lander, H. M. (1997). An essential role for free radicals and derived species in signal transduction. FASEB J. 11, 118-124
52. Larson, O. (1987). Role of biosynthesis of cholesterol and isoprenoid derivatives in regulation of Gl progression and cell proliferation of 356 cells. J. Cell. Phys. Biol. 133, 163-168
53. Lavallee, B, Provost, P. R, Roy, R, Gauthier, M. C, and Belanger, A. (1996). Dehydroepiandrosterone-fatty acid esters in human plasma: formation, transport and delivery to steroid target tissues. J. Endocrinol. 150, S119-S124
54. Leighton, B., Tagliaferro, A. R., and Newsholme, E. A. (1987). The effect of dehydroepiandrosterone acetate on liver peroxisomal enzyme activities of male and female rats. J. Nutr. 117, 1287-1290
55. Li, S., Yan, X., Belanger, A., and Labrie, F. (1993). Prevention by dehydroepiandrosterone of the development of mammary carcinoma induced by 7, 21-dimethylbenzfa]anthracene (DMBA) in the rat. Breast Cancer Res. Treat. 29, 203-217
56. Lu, L. J., Anderson, K. E., Grady, J. J., and Nagamani, M. (1996). Effects of soya consumption for one month on steroid hormones in premenopausal women: implications for breast cancer risk reduction. Cancer Epidem. Biomarker Prev. 5, 63-70
57. Luo, S., Sourla, A., Labrie, C., Belanger, A., and Labrie, F. (1997). Combined effects of dehydroepiandrosterone and EM-800 on bone mass, serum lipids, and the development of dimethylbenz[a]anthracene-induced mammary carcinoma in the rat. Endocrinology 138, 4435-4444
58. MacEwen, E. G, Maki-Haffa, A. L., and Kurzman, I. D. (1990). DHEA effects on cholesterol and lipoproteins. In: The Biologic Role of Dehydroepiandrosterone (DHEA), M. Kalimi and W. Regelson, eds. (Walter de Gruyter, Berlin), pp. 299-315
59. Maltese, W. A. (1990). Posttranslational modification of proteins by isoprenoids in mammalian cells. FASEB J. 4, 3319-3329
60. Marks, P. A. and Banks, J. (1960). Inhibition of mammalian glucose-6-phosphate dehydrogenase by steroids. Proc. Natl. Acad. Sei. USA45, 447-452
61. Massobrio, M, Migliardi, M, Cassoni, P., Menzaghi, C., Revelli, A., and Cenderelli, G. (1994). Steroid gradients across the cancerous breast: an index of altered steroid metabolism in breast cancer? J. Steroid Biochem. Molec. Biol. 57, 175-181
62. Mayer, D., Metzger, C., Leonetti, P., Beier, K., Benner, A., and Bannasch, P. (1998). Differential expression of key enzymes of energy metabolism in preneoplastic and neoplastic rat liver lesions induced by N-nitrosomorpholine and dehydroepiandrosterone. Int. J. Cancer 79, 232-240
63. Mayer, D., Reuter, S., Hoffmann, H., Bocker, T, and Bannasch, P. (1996). Dehydroepiandrosterone reduces expression of glycolytic and gluconeogenic enzymes in the liver of male and female rats. Int. J. Oncol. 8, 1069-1078
64. Mayer, D., Weber, E., and Bannasch, P. (1990). Modulation of liver carcinogenesis by dehydroepiandrosterone. In: The Biologic Role of Dehydroepiandrosterone (DHEA), M. Kalimi and W. Regelson, eds. (Walter de Gruyter, Berlin), pp. 361-385
65. Mayer, D., Weber, E., Moore, M. A., Letsch, I., Filsinger, E., and Bannasch, P. (1988). Dehydroepiandrosterone induced alterations in rat liver carbohydrate metabolism. Carcinogenesis 9, 2039-2043
66. McCormick, D. L, Rao, K. V. N., Johnson, W. D, Bowman-Gram, T. A., Steele, V. E, Lubet, R. A., and Kelloff, G. J. (1996). Exceptional chemopreventive activity of low-dose dehydroepiandrosterone in the rat mammary gland. Cancer Res. 56, 1724-1726
67. Metherall, J. E., Goldstein, J. L., Luskey, K. L., and Brown, M. S. (1989). Loss of transcriptional repression of three sterol-regulated genes in mutant hamster cells. J. Biol. Chem. 264, 15634-15641
68. Metzger, C., Bannasch, P., and Mayer, D. (1997). Enhancement and phenotypic modulation of N-nitrosomorpholine-induced hepatocarcinogenesis by dehydroepiandrosterone. Cancer Lett. 727, 125-131
69. Metzger, C., Mayer, D., Hoffmann, H., Bocker, T., Hobe, G., Benner, A., and Bannasch, P. (1995). Sequential appearance and ultrastructure of amphophilic cell foci, adenomas, and carcinomas in the liver of male and female rats treated with dehydroepiandrosterone. Toxicol. Pathol. 23, 591-605
70. Mohan, P. F. and Cleary, M. P. (1992). Studies on nuclear binding of dehydroepiandrosterone in hepatocytes. Steroids 57, 244-247
71. Moore, M., Weber, E., and Bannasch, P. (1988). Modulating influence of dehydroepiandrosterone administration on the morphology and enzyme phenotype of dimethylaminoazobenzene-induced hepatocellular foci and nodules. Vichows Arch. B 55, 337-343
72. Moore, M. A., Thamavit, W., Tsuda, H., Sato, K., Ichihara, A., and Ito, N. (1986). Modifying influence of dehydroepiandrosterone on the development of dihydroxy-di-w-propylnitrosamine-initiated lesions in the thyroid, lung and liver of F344 rats. Carcinogenesis 7, 311-316
73. Moore, M. A., Weber, E, Thornton, M., and Bannasch, P. (1988). Sex-dependent, tissue-specific opposing effect of dehydroepiandrosterone on initiation and modulation stages of liver and lung carcinogenesis induced by dihydroxy-di-n-propylnitrosamine in F344 rats. Carcinogenesis 9, 1507-1509
74. Najid, A. and Habrioux, G. (1990). Biological effects of adrenal androgens on MKCF-7 and BT-20 human breast cancer cells. Oncology 47, 269-274
75. Ogiu, T., Hard, G. C., Schwartz, A. G., and Magee, P. N. (1990). Investigation into the effect of DHEA on renal carcinogenesis induced in rat by single dose of DMN. Nutr. and Cancer 14, 57-67
76. Omer, G. A., Donohoe, R. M, Hendricks, J. D, Curtis, L. R, and Williams, D. E. (1996). Comparison of the enhancing effects of dehydroepiandrosterone with the structural analog 16-α-fluoro-5-androsten-17-one on aflatoxin BI hepatocarcinogenesis in rainbow trout. Fund. Appl. Toxicol. 34, 132-140
77. Omer, G. A., Mathews, C, Hendricks, J. D., Carpenter, H. M, Bailey, G. S., and Williams, D. E. (1995). Dehydroepiandrosterone is a complete hepatocarcinogen and potent tumor promoter in the absence of peroxisome proliferation in rainbow trout. Carcinogenesis 76, 2893-2898
78. Pascale, R. M., Garcea, R., Ruggiu, M. E., Frassetto, S., Vannini, M. G., Cozzolino, P., Lenzerini, L., Feo, F., and Schwartz, A. G. (1987). Decreased stimulation by 12-0-tetradecanoyl-phorbol-13-acetate of superoxide radical production by polymorphonuclear leukocytes carrying the Mediterranean variant of glucose-6-phosphate dehydrogenase. Carcinogenesis 8, 1567-1570
79. Pascale, R. M., Simile, M. M., and Feo, F. (1993). Genomic abnormalities in hepatocarcinogenesis. Implications for a chemopreventive strategy. Anticancer Res. 13, 1341-1356
80. Pascale, R. M, Simile, M. M, De Miglio, M. R, Nufris, A., Seddaiu, M. A., Muroni, M. R., Danni, O., Rao, K. N, and Feo, F. (1995). Inhibition of 3-hydroxy-3-methylglutaryl-CoA reductase activity and gene expression by dehydroepiandrosterone in preneoplastic liver nodules. Carcinogenesis 16, 1537-1542
81. Pashko, L. L., Hard, G. C, Rovito, R. J., Williams, J. R., Sobel, E. L, and Schwartz, A. G. (1985). Inhibition of 7, 12-dimethylbenz[a]anthracene-induced skin papillomas and carcinomas by dehydroepiandrosterone and 3β-methylandrost-5-en-17-one in mice. Cancer Res. 45, 164-166
82. Pashko, L. L., Lewbart, M. L., and Schwartz, A. G. (1991). Inhibition of 12-0-tetradecanoylphorbol-13-acetate-promoted skin tumor formation in mice by 16-a-fluoro-5-androsten-l 7-one and its reversal by deoxyribonucleosides. Carcinogenesis 12, 2189-2192
83. Pashko, L. L., Rovito, R. J., Williams, J. R., Sobel, E. L., and Schwartz, A. G. (1984). Dehydroepiandrosterone (DHEA) and 3β-methylandrost-5-en-17-one: inhibitors of 7, 12-dimethylbenz[a]anthracene (DMBA)-induced and 12-O-tetradecanoylphorbol-13-acetate (TPA)-promoted skin papilloma formation in mice. Carcinogenesis 5, 463-466
84. Pasqualini, J. R. (1993). Role of androgens in breast cancer. J. Steroid Biochem. Molec. Biol. 45, 167-172
85. Pereira, M. A. and Khoury, M. D. (1991). Prevention by chemopreventi ve agents of azoxymethane-induced foci of aberrant crypts in rat colon. Cancer Lett. 61, 27-33
86. Perkins, S. N, Hursting, S. D, Haines, D. C., James, S. J., Miller, B. J., and Phang, J. M. (1997). Chemoprevention of spontaneous tumorigenesis in nullizygous p53-deficient mice by dehydroepiandrosterone and its analog 16(-fluoro-5-androsten-l 7-one. Carcinogenesis 18, 989-994
87. Peters, J. M, Zhou, Y. C, Ram, P. A., Lee, S. S. T, Gonsalez, F. J., and Waxman, D. J. (1996). Peroxisome proliferator activated receptor alpha required for gene induction by dehydroepiandrosterone 3-beta-sulfate. Mol. Pharmacol. 50, 67-74
88. Poortman, J., Prenen, J, Schwarz, F., and Thijssen, J. (1975). Interaction of 5-en-androstene-3β-17β-diol with estradiol and dihydrotestosterone receptors in human myometrial and mammary cancer tissue. J. Clin. Endocrinol. Metab. 40, 373-379
89. Prasanna, H. R, Lu, M. H, Beland, F. A., and Hart, R. W. (1989). Inhibition of Aflatoxin B, binding to hepatic DNA by dehydroepiandrosterone in vivo. Carcinogenesis 10, 2197-2200
90. Prough, R. A., Webb, S. J., Wu, H.-Q., Lapenson, D. P., and Waxman, D. J. (1994). Induction of microsomal and peroxisomal enzymes by dehydroepiandrosterone and its reduced metabolite in rats. Cancer Res. 54, 2878-2886
91. Prough, R. A., Wu, H.-Q., and Milewich, L. (1990). Effect of dehydroepiandrosterone on rodent liver microsomal, mitochondrial, and peroxisomal proteins. In: The Biologic Role of Dehydroepiandrosterone (DHEA), M. Kalimi and W. Regelson, eds. (Walter de Gruyter, Berlin), pp. 253-279
92. Quesney-Huneenus, V., Wiley, M. H., and Siperstein, M. D. (1979). Essential role of mevalonate synthesis in DNA replication. Proc. Natl. Acad. Sei. USA 76, 5056-5060
93. Ram, P. A. and Waxman, D. J. (1994). Dehydroepiandrosterone 3β-sulfate is an endogenous activator of the peroxisome-proliferation pathway: induction of cytochrome P-450 4A and acyl-CoA oxidase mRNAs in primary rat hepatocyte culture and inhibitory effects of Ca2+-channel blockers. Biochem. J. 301, 753-758
94. Rao, A. R. (1989). Inhibitory action of dehydroepiandrosterone on methylcholanthrene-induced carcinogenesis in the uterine cervix of mouse. Cancer Lett. 45, 1-5
95. Rao, K. N. (1986). Regulatory aspects of cholesterol metabolism in cells with different degrees of replication. Toxicol. Pathol. 14, 430-437
96. Rao, M. S., Reid, B., Ide, H., Subbaro, V., and Reddy, J. K. (1994). Dehydroepiandrosterone-induced peroxisome proliferation in the rat: evaluation of sex differences. Proc. Soc. Exptl. Biol. Med. 207, 186-190
97. Rao, M. S., Subbarao, V., Yeldandi, A. V., and Reddy, J. K. (1992). Hepatocarcinogenicity of dehydroepiandrosterone in the rat. Cancer Res. 52, 2977-2979
98. Ratko, T. A., Detrisac, C. J., Mehta, R. G., Kelloff, G. J., and Moon, R. C. (1991). Inhibition of rat mammary gland chemical carcinogenesis by dietary dehydroepiandrosterone or a fluorinated analogue of dehydroepiandrosterone. Cancer Res. 51, 481-486
99. Ruis-Larrea, M. B., Leal, A. M., Martin, C., Martinez, R., and Lacort, M. (1995). Effects of estrogens on the redox chemistry iron: a possible mechanism of the antioxidant action of estrogens. Steroids 60, 780-783
100. Sargent, L., Gragan, Y., Xu, Y.-H., Sattler, G, Wiley, J., and Pitot, H. C. (1996). Karyotypic changes in a multistage model of chemical hepatocarcinogenesis in the rat. Cancer Res. 56, 2985-2991
101. Schulz, S. and Nyce, J. W. (1991). Inhibition of protein isoprenylation and p21ras membrane association by dehydroepiandrosterone in human colonic adenocarcinoma cells in vitro. Cancer Res. 51, 6563-6567
102. Schulz, S, Klann, R. C, Schönfeld, S, and Nyce, J. W. (1992). Mechanism of cell growth inhibition and cell cycle arrest in human colonic adenocarcinoma cells by dehydroepiandrosterone: role of isoprenoid biosynthesis. Cancer Res. 52, 1372-1376
103. Schwartz, A.G. (1979). Inhibition of spontaneous breast cancer formation in female C3H (Avy/a) mice by long-term treatment with dehydroepiandrosterone. Cancer Res. 15, 1269-1274
104. Schwartz, A.G. and Pashko, L.L. (1993). Cancer chemoprevention with the adrenocortical steroid dehydroepiandrosterone and structural analogs. J. Cell. Biochem. 17G, 73-79
105. Schwartz, A.G. and Pashko, L.L. (1995). Cancer prevention with dehydroepiandrosterone and non-androgenic structural analogs. J. Cell. Biochem. 22, s210-s217
106. Schwartz, A.G. and Perantoni, A. (1975). Protective effect of dehydroepiandrosterone against aflatoxin 1 and 7, 12-dimethylbenzanthracene-induced cytotoxicity and transformation in cultured cells. Cancer Res. 35, 2482-2487
107. Schwartz, A.G. and Tannen, R.H. (1981). Inhibition of 7, 12 dimethylbenz[a]anthracene and urethane-induced lung tumor formation in A/J mice by long-term treatment with dehydroepiandrosterone. Carcinogenesis 2, 1335-1337
108. Schwartz, A.G., Fairman, D.K., Polansky, M, Lewbart, M.L., and Pashko, L.L. (1989). Inhibition of 7, 12-dimethylbenz[a]anthracene-initiated and 12-O-tetradecanoylphorbol-13-acetate-promoted skin papilloma formation in mice by dehydroepiandrosterone and two synthetic analogs. Carcinogenesis 10, 1809-1813
109. Schwartz, A.G., Lewbart, M.L.K., and Pashko, L.L. (1988). Novel dehydroepiandrosterone analogous with enhanced biological activity and reduced side-effects in mice and rats. Cancer Res. 48, 4817-4822
110. Schwartz, A.G., Whitcomb, J.M., Nyce, J. W., Lewhart, M.L., and Pashko, L.L. (1988). Dehydroepiandrosterone and structural analogs: a new class of cancer chemopreventive agents. Adv. Cancer Res. 51, 391-424
111. Secreto, G., Toniolo, P., Berrino, F., Recchiome, C., Cavalleri, P., Pisani, P., Totis, A., Fariselli, G., and Pietro, S. (1991). Serum and urinary androgens and risk of breast cancer in postmenopausal women. Cancer Res. 51, 2572-2576
112. Shepherd, A. and Cleary, P. (1984). Metabolic alterations after dehydroepiandrosterone treatments in Zucker rats. Am. J. Physiol. 246, 123-128
113. Shibata, M.-A., Hasegawa, R., Imaida, K., Hagiwara, A., Ogawa, K., Hirose, M., Ito, N., and Shirai, T. (1995). Chemoprevention by dehydroepiandrosterone and indonethacin in a rat multiorgan carcinogenesis model. Cancer Res. 55, 4870-4874
114. Shibata, M.-A., Shirai, T., Asakawa, E, Hirose, M., and Fukushima, S. (1993). Inhibition by dehydroepiandrosterone of butylated hydroxyanisole (BHA) promotion of rat-bladder carcinogenesis and enhancement of BHA-induced forestomach hyperplasia. Int. J. Cancer 53, 819-823
115. Simile, M. M., Pascale, R. M, De Miglio, M. R, Nufris, A., Daino, L., Seddaiu, M. A., Muroni, M. R., Rao, K. N., and Feo, F. (1995). Inhibition by dehydroepiandrosterone of growth and progression of persistent liver nodules in experimental rat liver carcinogenesis. Int. J. Cancer 62, 210-215
116. Solt, D. B, Medline, A., and Farber, E. (1977). Rapid emergence of carcinogen-induced hyperplastic lesions in a new model for the sequential analysis of liver carcinogenesis. Am. J. Pathol. 88, 595-618
117. Song, M. K. H., Grieco, D, Rail, J. E., and Nikodem, W. M. (1989). Thyroid hormone-mediated transcriptional activation of the rat liver malic enzyme gene by dehydroepiandrosterone. J. Biol. Chem. 264, 18981-18985
118. Swierczynski, J. and Mayer, D. (1996). Dehydroepiandrosterone-induced lipid peroxidation in rat liver mitochondria. J. Steroid Biochem. Molec. Biol. 58, 599-603
119. Swierczynski, J., Bannasch, P., and Mayer, D. (1996). Increase of lipid peroxidation in rat liver microsomes by dehydroepiandrosterone feeding. Biochim. Biophys. Acta 1315, 193-198
120. Swierczynski, J., Kochan, Z., and Mayer, D. (1997). Dietary (-tocopherol prevents dehydroepiandrosteroneinduced lipid peroxidation in rat liver microsomes and mitochondria. Toxicol. Lett. 91, 129-136
121. Tagliaferro, A. R., Davis, J. R., Truchon, S., and van Hamont, N. (1986). Effects of dehydroepiandrosterone acetate on metabolism, body weight and composition of male and female rats. J. Nutr. 116, 1977-1983
122. Tagliaferro, A. R, Roebuck, B. D., Ronan, A. M., and Meeker, L. D. (1992). Enhancement of pancreatic carcinogenesis by dehydroepiandrosterone. Ad. Exptl. Med. Biol. 322, 119-129
123. Tamagno, E, Aragno, M, Boccuzzi, G., Gallo, M, Parola, S., Fubini, B, Poli, and Danni, O. (1998). Oxygen free radical scavenger properties of dehydroepiandrosterone. Cell. Biochem. Funct. 16, 57-63
124. Tepperman, H. M., De la Garza, S. A., and Tepperman, J. (1968). Effect of dehydroepiandrosterone and diet protein on liver enzymes and lipogenesis. Am. J. Physiol. 214, 1126-1132
125. Theriault, C. and Labrie, F. (1991). Multiple steroid metabolic pathways in ZR-75-1 human breast cancer cells. J. Steroid Biochem. Molec. Biol. 38, 155-164
126. Thornton, M., Moore, M. A., and Ito, N. (1989). Modifying influence of dehydroepiandrosterone or butylated hydroxytoluene treatment on initiation and development stages of azaserine-induced acinar pancreatic lesions in the rat. Carcinogenesis 10, 407-410
127. Van Werden, E.-M., Bierings, H. G, van Steenbrugge, G. J., de Jong, F. H, and Schröder, F. H. (1992). Adrenal glands of the mouse and rat do not synthesize androgens. Life Sei. 50, 857-861
128. Wang, D. Y., Bulbrook, R. D., Herian, M., and Hayward, J. L. (1974). Studies on the sulphate esters of dehydroepiandrosterone and androsterone in the blood of women with breast cancer. Eur. J. Cancer 10, 477-482
129. Waxman, D. J. (1996). Role of metabolism in the activation of dehydroepiandrosterone as a peroxisome proliferator. J. Endrocrinol. 150, S129-S147
130. Weber, E., Moore, M., and Bannasch, P. (1988). Phenotypic modulation of hepatocarcinogenesis and reduction in /V-nitrosomorpholine-induced hemangiosarcoma and adrenal lesion development in Sprague-Dowley rats by dehydroepiandrosterone. Carcinogenesis 9, 1191-1195
131. Whitcomb, J. M. and Schwartz, A. G. (1985). Dehydroepiandrosterone and 16-Br-epiandrosterone inhibit 12-O-tetradecanoyl-phorbol-13-acetate stimulation of superoxide radical production by human polymorphonuclear leukocytes. Carcinogenesis 6, 333-335
132. Wilmer, J. S. and Foster, T. S. (1965). The influence of dehydroepiandrosterone and pregnenolone upon adaption of hepatic glucose-6-phosphate dehydrogenase to refeeding a high-glucose diet after fasting. Can. J. Biochem. 43, 1375-1377
133. Wu, H.-Q., Massett-Brown, J., Tweedie, D.J., Milewich, L., Frenkel, R.A., Martin-Wixtrom, C, Estrabrook, R.W., and Prough, R.A. (1989). Induction of microsomal NADPH-cytochrome P-450 reductase and cytochrome P450IVA1 (P-450LAto) by dehydroepiandrosterone in rats: a possible peroxisomal proliferator. Cancer Res. 49, 2337-2343
134. Yamada, J., Sakuma, M., and Suga, T. (1992). Induction of peroxisomal β-oxidation enzymes by dehydroepiandrosterone and its sulfate in primary cultures of rat hepatocytes. Biochim. Biophys. Acta 1137, 231-236
135. Yamada, Y., Sakuma, M., Ikeda, T., Fukuda, K., and Suga, T. (1991). Characteristics of dehydroepiandrosterone as a peroxisomal proliferator. Biochim. Biophys. Acta 1092, 233-243
136. Zhang, H., Tamura, H., Yamada, J., Watanabe, T., and Suga, T. (1996). Effect of nicardipine calcium antagonist, on induction of peroxisomal enzymes by dehydroepiandrosterone sulfate in cultured rat hepatocytes. J. Toxicological. Sei. 21, 235-241
137. Zeleniuch-Jacquotte, A., Brüning, P. F., Bonfrer, J. M, Koenig, K. L, Shore, R., Kin, M. Y, Pasternack, B. S, and Toniolo, P. (1997). Relation of serum levels of testosterone and dehydroepiandrosterone sulfate to risk of breast cancer in postmenopausal women. Am. J. Epidemiol. 145, 1030-1038
138. Nyce, J. W., Magee, P. N., Hard, J. C., and Schwartz, A. G. (1984). Inhibition of 1, 2-dimethylhydrazine-induced colon tumorigenesis in Balb/c mice by dehydroepiandrosterone. Carcinogenesis 5, 57-62