Androgenic profile and genotoxicity evaluation of testosterone propionate and novel synthesized heterocyclic steroids.
In this study, we tested the androgenic activity of three structurally promising novel synthesized heterocyclic steroids compared with testosterone propionate in male mice. Additionally, the possible genotoxic effects of the novel synthesized heterocyclic steroids in comparison with testosterone propionate on male mice using chromosomal analysis of somatic and germ cells as well as RAPD-PCR were investigated. Male mice were administered with two doses of testosterone propionate, pyridoandrostene derivative 4b, pyrimidinoandrostene derivative 9a and thienoandrostene derivative 12 (200 and 400mg/kg b.w.) daily for 2 weeks. Results indicated that compounds 4b and 12 have androgenic activity as well as testosterone propionate. There were no significant differences in the frequencies of total chromosomal aberrations in both somatic and germ cells as well as no alteration in the DNA bands patterns between control, testosterone propionate and pyridoandrostene 4b treated animals. However, the pyrimidinoandrostene derivative 9a caused significant increase in the mean value of total chromosomal aberrations of both somatic and germ cells (P< or =0.01) as well as enhanced the polymorphic bands patterns as compared to the control and the other tested compounds. On the other hand, thienoandrostene derivative 12 induced significant decrease in the mean values of chromosomal aberrations in both somatic and germ cells, decreased sperm morphological abnormalities, increased the sperm count and motility than control. Our data indicate that testosterone propionate; pyridoandrostene 4b and thienoandrostene derivative 12 have no genotoxic activity. However, pyrimidinoandrostene derivative 9a has genotoxic activity possibly due to a modulation of the different expression of the catalyzing enzyme systems which will be investigated in the nearly future.
Hana
Hanaa Y
HY
Hormones Department, National Research Center, 12622 Dokki, Cairo, Egypt.
Khalil
Wagdy K B
WK
Elmakawy
Aida I
AI
Elmegeed
Gamal A
GA
D000728:Androgens / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity; D000818:Animals; D002869:Chromosome Aberrations / Q000139:chemically induced; D004249:DNA Damage; D053938:DNA Fragmentation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D008297:Male; D051379:Mice; D008954:Models, Biological; D011485:Protein Binding; D011944:Receptors, Androgen / Q000378:metabolism; D013094:Spermatozoa / Q000187:drug effects; D013256:Steroids / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D013737:Testis / Q000187:drug effects*; D043343:Testosterone Propionate / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*
D000728:Androgens; D006571:Heterocyclic Compounds; D011944:Receptors, Androgen; D013256:Steroids; D043343:Testosterone Propionate