Steroidal drug cyproterone acetate is activated to DNA-binding metabolites by sulfonation

Cancer Research

Volumn 56, Issue 19, 1996, Pages 4391-4397

  Werner, Silke ^a   Kunz, Susanne ^a   Wolff, Thomas ^a   Schwarz, Leslie R ^a  

^a INSTITUTE OF EPIDEMIOLOGY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CYPROTERONE ACETATE;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; CELL FRACTIONATION; DNA ADDUCT; DNA BINDING; DRUG ACTIVITY; FEMALE; GENOTOXICITY; LIVER CELL; NONHUMAN; PRIORITY JOURNAL; PROSTATE CANCER; RAT;

ANIMALS; BIOTRANSFORMATION; CYPROTERONE ACETATE; CYTOSOL; DNA; DNA ADDUCTS; FEMALE; LIVER; MALE; NAD; NADP; OXIDOREDUCTASES; PRODRUGS; RATS; RATS, WISTAR; SULFOTRANSFERASES;

EID: 0029783632     PISSN: 00085472     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (45)

1. Neumann, I , Thierau, D., Andrae, U , Greim, H., and Schwarz, L R. Cyproterone acetate induces DNA damage in cultured rat hepatocytes and preferentially stimulates DNA synthesis in γ-glutamyltranspeptidase-positive cells. Carcinogenesis (Lond.), 13: 373-378, 1992
2. Topinka, J., Andrae, U, Schwarz, L. R., and Wolff, T. Cyproterone acetate generates DNA adducts in rat liver and in primary rat hepatocyte cultures. Carcinogenesis (Lond ), 14. 423-427, 1993.
3. Schwarz, L. R., Werner, S., Topinka, J., Andrae, U , Neumann, I , and Wolff, T. The liver as origin and target of reactive intermediates exemplified by the progesterone derivative, cyproterone acetate. In: R. Snyder J. J Kocsis, I. G. Sipes, G. F. Kalf, D. J. Jollow, H. Greim, T. J. Monks, and C. M. Witmer (eds ), Biological Reactive Intermediates: V. Basic Mechanistic Research in Toxicology and Human Risk Assessment, pp 243-251. New York: Plemum Press, 1996.
4. Martelli, A., Mattioli, F., Fazio, S., Andrae, U., and Brambilla, G. DNA repair synthesis and DNA fragmentation in primary cultures of human and rat hepatocytes exposed to cyproterone acetate. Carcinogenesis (Lond ), 16 1265-1269, 1995.
5. Schuppler, J., and Günzel, P Liver tumors and steroid hormones in rats and mice. Arch. Toxicol. Suppl. 2: 181-195, 1979.
6. Schulte-Hermann, R., Ohde, G., Schuppler, J., and Timmermann-Trosiener, I Enhanced proliferation of putative preneoplastic cells in rat liver following treatment with the tumor promoters phenobarbital, hexachlorocyclohexane, steroid compounds, and nafenopin. Cancer Res., 41 2556-2562, 1981
7. Schulte-Hermann, R , Timmermann-Trosiener, I , and Schuppler, J Promotion of spontaneous preneoplastic cells in rat liver as a possible explanation of tumor production by nonmutagenic compounds. Cancer Res., 43: 839-844, 1983.
8. Parzefall, W., Monschau, P., and Schulte-Hermann, R Induction by cyproterone acetate of DNA synthesis and mitosis in primary cultures of adult rat hepatocytes in serum-free medium Arch. Toxicol., 63. 456-461, 1989.
9. Schulte-Hermann, R , Ochs, H., Bursch, W., and Parzefall, W. Quantitative structure-activity studies on effects of sixteen different steroids on growth and monooxygenases of rat liver Cancer Res , 48: 2462-2468, 1988.
10. Bursch, W , Lauer, B., Timmermann-Trosiener, I. Barthel, G., Schuppler, J , and Schulte-Hermann, R. Controlled cell death (apoptosis) of normal and putative preneoplastic cells in rat liver following withdrawal of tumor promoters Carcinogenesis (Lond.), 5. 453-458, 1984.
11. Lang, R., and Redmann, U Non-mutagenicity of some sex hormones in the Ames Salmonella/microsome mutagenicity test. Mutat. Res., 67 361-365, 1979
12. Lang, R., and Reimann, R. Studies for a genotoxic potential of some endogenous and exogenous sex steroids. I Communication: examination for the induction of gene mutations using the Ames Salmonella/microsome test and the HGPRT test in V79 cells. Environ. Mol. Mutagen., 21: 272-304, 1993.
13. Topinka, J., Binkova, B., Zhu, H K., Andrae, U., Neumann, I., Schwarz, L. R., Werner, S., and Wolff, T. DNA damaging activity of the cyproterone acetate analogues chlormadinone acetate and megestrol acetate in rat liver. Carcinogenesis (Lond.), 16: 1483-1487, 1995.
14. Werner, S., Topinka, J., Kunz, S , Beckurts, T., Heidecke, C-D., Schwarz, L. R , and Wolff, T Studies on the formation of hepatic DNA adducts by the antiandrogenic and gestagenic drug, cyproterone acetate. In: R. Snyder J. J Kocsis, I G Sipes, G. F. Kalf, D. J Jollow, H. Greim, T. J. Monks, and C M. Witmer (eds ), Biological Reactive Intermediates: V. Basic Mechanistic Research in Toxicology and Human Risk Assessment, pp. 253-257 New York: Plemum Press, 1996.
15. Werner, S , Topinka, J., Wolff, T., and Schwarz, L R. Accumulation and persistence of DNA adducts of the synthetic steroid cyproterone acetate in rat liver. Carcinogenesis (Lond.), 16: 2369-2372, 1995
16. Demi, E., Schwarz, L R., and Oesterle, D. Initiation of enzyme-altered foci by the synthetic steroid cyproterone acetate in rat liver foci bioassay. Carcinogenesis (Lond), 14: 1229-1231, 1993.
17. Kerdar, R. S., Baumann, A., Brudny-Klöppel, M., Biere, H., Blode, H., and Kuhnz, W. Identification of 3α-hydroxy-cyproterone acetate as a metabolite of cyproterone acetate in the bile of female rats and the potential of this and other already known or putative metabolites to form DNA adducts in vitro. Carcinogenesis (Lond.), 16: 1835-1841, 1995.
18. Schwarz, L R., and Watkins, J B. Uptake of taurocholate, a vecuronium like organic cation. ORG 9426, and oubain into carcinogen-induced diploid and polyploid hepatocytes obtained by centrifugal elutriation. Biochem. Pharmacol., 43: 1195-1201, 1992.
19. Remmer, H., Greim, H , Schenkman, J. B , and Estabrook, R. W. Methods for the elevation of hepatic microsomal mixed function oxidases levels and cytochrome P-450. Methods Enzymol. 10: 703-708, 1967
20. 32P-postlabeling analysis of aromatic carcinogen adducts. Cancer Res., 45. 5656-5662, 1985.
21. Gupta, R. C., and Dighe, N. R. Formation and removal of DNA adducts in rat liver treated with N-hydroxy derivatives of 2-acetylaminofluorene, 4-acetylaminobiphenyl and 2-acetylaminophenanthrene. Carcinogenesis (Lond.), 5: 343-349, 1984
22. Mulder. G J. Sulfate availability in vivo. In: G J. Mulder (ed.), Sulfation of Drugs and Related Compounds, pp. 31-52. Boca Raton: CRC Press, 1981.
23. Schwarz, L. R. Modulation of sulfation and glucuronidation of 1-naphthol in isolated rat liver cells. Arch Toxicol , 44: 137-145, 1980.
24. Schwarz, L. R. Sulfation of 1-naphthol in isolated rat hepatocytes Hoppe-Seyler's Z Pnysiol. Chem., 365: 43-48, 1984
25. Okuda, H , Nojima, H., Watanabe, N., and Watabe, T. Sulphotransferase-mediated activation of the carcinogen 5-hydroxymethyl-chrysene. Biochem Pharmacol , 38 3003-3009, 1989.
26. Falany, C. N., and Wilborn, T. W. Biochemistry of cytosolic sulfotransferases involved in bioactivation. In: M. W. Anders and W. Dekant (eds.), Advances in Pharmacology, vol. 27 Conjugation-dependent Carcmogenicity and Toxicity of Foreign Compounds, pp. 301-329 San Diego. Academic Press, 1994.
27. Ottemess, D. M., Wieben, E. D., Wood, T. C., Watson, R. W. G., Madden, B. J. McCormick, D. J., and Weinshilboum, R. M. Human liver dehydroepiandrosterone sulfotransferase: molecular cloning and expression of cDNA. Mol. Pharmacol., 41: 865-872, 1992.
28. Lee, Y. C , Park, C-S., and Strott, C. A Molecular cloning of a chiral-specific 3α-hydroxysteroid sulfotransferase J Biol. Chem , 269: 15838-15845, 1994
29. Hobkirk, R Steroid sulfation. Trends Endocrinol. Metab., 4: 69-74, 1993.
30. King, C. M , and Phillips, B. Enzyme-catalyzed reactions of the carcinogen N-hydroxy-2-fluorenylacetamide with nucleic acid. Science (Washington DC), 159: 1351-1353, 1968
31. DeBraun, J. R., Rowley, J. Y., Miller, E C , and Miller, J. A. Sulfotransferase activation of N-hydroxy-2-acetylaminofluorene in rodent livers susceptible and resistant to this carcinogen Proc. Soc. Exp. Biol. Med., 129: 268-273, 1968
32. Miller, J A. Sulfonation in chemical carcinogenesis - history and present status Chem Biol Interact , 92: 329-341. 1994
33. Glatt, H , Seidel, A , Harvey, R. G , and Coughtrie, W. H. Activation of benzylic alcohols to mutagens by human hepatic sulfotransferases Mutagenesis, 9: 553-557, 1994.
34. Glatt, H , Pauly, K , Frank, H , Seidel, A , Oesch, F., Harvey, R. G., and Werle-Schneider, G Substance-dependent sex differences in the activation of benzylic alcohols to mutagens by hepatic sulfotransferases of the rat. Carcinogenesis (Lond ). 15 2605-2611, 1994
35. Hobkirk, R Steroid sulfotransferases and steroid sulfate sulfatases: characteristics and biological roles Can J. Biochem Cell Biol , 63: 1127-1144, 1985
36. Watabe, T . Ogura, K., Satsukawa. M., Okuda, H., and Hiratsuka, A. Molecular cloning and functions of rat liver hydroxysteroid sulfotransferases catalysing covalent binding of carcinogenic polycyclic arylmethanols to DNA Chem. Biol. Interact., 92: 87-105, 1994
37. Homma, H , Nakagome, I , Kamakura, M , Hirota, M., Takahashi, M , and Matsui, M. Studies on rat hepatic hydroxysteroid sulfotransferase - immunochemistry, development and pI variants Chem Biol. Interact , 92: 15-24, 1994
38. Demyan, W. F., Song, C. S. Kim, D S., Her, S., Gallwitz, W , Rao, T. R. Slomczynska. M., Chatterjee, B., and Roy, A. K. Estrogen sulfotransferase of the rat liver complementary DNA cloning and age-specific and sex-specific regulation of messenger RNA. Mol. Endocrinol., 6: 589-597, 1992.
39. Nagata, K., Ozawa, S., Miyata, M., Shimadzu, M , Gong, D. W , Yamazoe, Y., and Kato, R. Isolation and expression of a cDNA encoding a male specific rat sulfotransferase that catalyses activation of N-hydroxy-2-acetylaminofluorene J. Biol Chem., 268: 24720-24725, 1993.
40. Topinka, J., Schwarz, L. R., Werner, S , Sram, R J , and Wolff, T. Persistence and accumulation of DNA adducts induced by the synthetic steroid cyproterone acetate in rat liver in vivo (Abstract). 23rd Annual Meeting of the European Enviromental Mutagen Society, Barcelona, September 27-October 2, 1993, p. 215.
41. Aksoy, I. A , Sochorova, V., and Weinshilboum, R. Human liver dehydroepiandrosterone sulfotransferase: nature and extent of individual variation Clin Pharmacol. Ther., 54. 498-506, 1993.
42. Glatt, H., Henschler, R., Philipps, D H., Blake, J. W., Steinberg, P., Seidel, A , and Oesch, F Sulfotransferase-mediated chlorination of 1-hydroxymethylpyrene to a mutagen capable of penetrating indicator cells. Environ. Health Perspect., 88: 43-48, 1990.
43. Maser, E. Xenobiotic carbonyl reduction and physiological steroid oxidoreduction. Biochem. Pharmacol., 49: 421-440, 1995.
44. 32P-postlabeling and use of metabolic inhibitors for two distinct pathways leading to mouse hepatic DNA adduct formation and identification of 4-hydroxytamoxifen. Carcinogenesis (Lond.). 15 2087-2094, 1994.
45. 32P-postlabeling and use of pentachlorophenol for a novel metabolic activation pathway of diethylstilbestrol and us dimethyl ether in mouse liver likely α-hydroxylation of ethyl group(s) followed by sulfate conjugation Carcinogenesis (Lond.), 16. 2643-2648, 1995.