Calderón GD, Bratoeff TE, Ramírez LE, Dorado GV, Hernández GE, Trujillo JF

Language: Spanish
References: 21
Page: 156-159
PDF size: 110.20 Kb.

ABSTRACT

Synthetic progestins are used in different types of cancer and hormonal replacement therapy, and in recent studies they have been linked to DNA adduct formation in steroid therapies. The purpose of the present study was to evaluate the antimutagenic activity of a new synthetic neurosteroid, 3α-acetoxy-5,6-epoxy-16-pregnen-20-one, that altered 5-HIAA levels on the brain in previous studies. Its anti-mutagenic activity was evaluated by Ames assay using Salmonella typhimurium strains TA98 and TA100; A range of 1ng-1mg doses were evaluated. It was found that 3α-acetoxy-5,6-epoxy-16-pregnen-20-one showed slight toxicity against the TA100 strain in the maximum concentration (1mg/plate) and did not show mutagenicity in this test system with any of the doses evaluated. These results suggest that 3á-acetoxy-5,6-epoxy-16-pregnen-20-one did not possess mutagenic activity and might be useful as a promising candidate for new applications in human healthcare.

REFERENCES

1. Robel E, Baulieu EE. Neurosteroids: biosynthesis and function. Trends Endocrinol Metab 1994; 5:1-8.

2. Calderón GD, Barragán MG, Espitia VI, Hernández GE, Santamaría AD, Juárez OH. Effect of testosterone and steroids homologues on indolamines and lipid peroxidation in rat brain. J Steroid Biochem Mol Biol 2005; 94:369-73.

3. Hirosumi J, Nakayama O, Fagan T. FK143 a novel nonsteroidal inhibitor of steroid 5α-reductase: in vitro effects on human and animal prostatic enzymes. J Steroid Biochem Mol Biol 1995; 52:357-63.

4. McCarthy MM, Schwarz JM, Wright CL, Dean SL. Mechanisms mediating oestradiol modulation of the developing brain. J Neuroendocrinol 2008; 20(6):777-83.

5. Raynaud JP, Fiet J, Le Goff JM, Martin PM, Moguilewsky M, Ojasoo T. Design of antiandrogen and their mechanisms of action: A case study (Anandron). Hormone Res 1987; 28:230-41.

6. Flores E, Bratoeff E, Cabeza M, Ramírez E, Quiroz A, Heuze I. Steroid 5alpha-reductase inhibitors. Mini Rev Med Chem 2003; 3(3):225-37.

7. Calderón GD, Bratoeff E, Ramírez LE, Osnaya BN, García AR, Barragán MG, Hernández GE, Juárez OH. Effects of two new steroids and cyproterone on some biomarkers of oxidative stress and serotonergic system on rat prostate and brain. Andrología 2009; 41:29-34.

8. Hinkel A, Berges RR, Pannek J, Achulze H, Senge T. Cyproterone acetate in the treatment of advanced prostatic cancer: retrospective analysis of liver toxicity in the long-term follow-up of 89 patients. Eur Urol 1996; 30(4):464-70.

9. Krebs O, Schafer B, Wolff T, Oesterle D, Deml E, Sund M, Favor J. The DNA damaging drug cyproterone acetate causes gene mutations and induces glutathine-S-transferase P in the liver of female Big Blue. Carcinogenesis 1998; 19(2): 241-5.

10. Siddique YH, Beg T, Afzal M. Protective effect of nordihydroguaiaretic acid (NDGA) against norgestrel induced genotoxic damage. Toxicol in vitro 2006; 20:227-33.

11. Siddique YH, Afzal M. Genotoxic potential of cyproterone acetate: a possible role of reactive oxygen species. Toxicol in vitro 2005; 19:63-8.

12. Fahrig R. Anti-mutagenic agents are also co-recombinogenic and can be converted into co-mutagens. Mutation Research 1996; 350:59-67.

13. Maron DM, Ames BN. Revised methods for the Salmonella mutagenicity test. Mutat Res 1983; 113:173-215.

14. Castilla SL. Estadística simplificada para la investigación en Ciencias de la Salud. Editorial Trillas. México, D.F. 1995.

15. Reddy DS. Mass spectrometric assay and physiologicalpharmacological activity of androgenic neurosteroids. Neurochem Int 2008; 52(4-5):541-53.

16. Bratoeff E, Ramirez E, Murillo E, Flores G, Cabeza M. Steroidal antiandrogens and 5alpha-reductase inhibitors. Curr Med Chem 1999; 6:1107-23.

17. Joosten HFP, Van Acker FAA, Van den Dobbelsteen DJ, Horbach GJMJ, Krajnc EI. Genotoxicity and hormonal steroids. Toxicology Letters 2004; 151:113-34.