Induction of chromosome aberrations in Syrian hamster renal cortical cells by various estrogens.
Estrogens, both natural and synthetic, have been implicated in carcinogenesis at different organ sites in a variety of animals, including man, for more than six decades. However, the molecular mechanism(s) involved in the carcinogenic action of estrogens still remains both controversial and elusive. Cytogenetic damage in the hamster kidney has been studied after in vivo treatment with either potent or weak estrogens for varying periods. Compared to age-matched untreated control, diethylstilbestrol (DES) treatment resulted in significant increases in the number of chromatid gaps and breaks, chromosome breaks, and endoreduplicated cells in hamster renal cortical cells. These chromosomal aberrations (CA) were cumulative with continued hormone exposure from 1.0 to 5.0 months. However, chromosome exchanges as a result of the breaks were not elevated. After 5.0 months of hormone treatment, potent estrogens such as 17 beta-estradiol and Moxestrol exhibited similar frequencies of CA in the hamster kidney to that found for DES, whereas weak estrogens such as 17 alpha-estradiol and beta-dienestrol exhibited CA frequencies that were not significantly different from untreated levels. Ethinylestradiol treatment for a similar period resulted in significant increases in chromatid gaps, although these did not evolve into increases in either chromatid or chromosome breaks, and in a rise in endoreduplicated cells. These results raise the possibility that the CA generated after estrogen treatment may be involved in renal tumorigenic processes.
Banerjee
S K
SK
University of Kansas Cancer Center, Department of Pharmacology, Kansas City.
Banerjee
S
S
Li
S A
SA
Li
J J
JJ
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D002869:Chromosome Aberrations; D006224:Cricetinae; D004028:Dienestrol; D004054:Diethylstilbestrol; D004305:Dose-Response Relationship, Drug; D004958:Estradiol; D004967:Estrogens / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000031:analogs & derivatives; D007672:Kidney Cortex / Q000166:cytology / Q000187:drug effects*; D007680:Kidney Neoplasms / Q000139:chemically induced*; D008297:Male; D008647:Mesocricetus; D009153:Mutagens / Q000633:toxicity*
D004967:Estrogens; D009153:Mutagens; D004997:Ethinyl Estradiol; D004958:Estradiol; C011310:moxestrol; D004054:Diethylstilbestrol; D004028:Dienestrol