INDUCTION OF CHROMOSOME-ABERRATIONS IN SYRIAN-HAMSTER RENAL CORTICAL-CELLS BY VARIOUS ESTROGENS

Estrogens, both natural and synthetic, have been implicated in carcino genesis at different organ sites in a variety of animals, including ma n, for more than six decades. However, the molecular mechanism(s) invo lved in the carcinogenic action of estrogens still remains both contro versial 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 controls, dieth ylstilbestrol (DES) treatment resulted in significant increases in the number of chromatid gaps and breaks, chromosome breaks, and endoredup licated cells in hamster renal cortical cells. These chromosomal aberr ations (CA) were cumulative with continued hormone exposure from 1.0 t o 5.0 months. However, chromosome exchanges as a result of the breaks were not elevated. After 5.0 months of hormone treatment, potent estro gens such as 17 beta-estradiol and Moxestrol exhibited similar frequen cies of CA in the hamster kidney to that found for DES, whereas weak e strogens such as 17 alpha-estradiol and beta-dienestrol exhibited CA f requencies that were not significantly different from untreated levels . Ethinylestradiol treatment for a similar period resulted in signific ant increases in chromatid gaps, although these did not evolve into in creases in either chromatid or chromosome breaks, and in a rise in end oreduplicated cells. These results raise the possibility that the CA g enerated after estrogen treatment may be involved in renal tumorigenic processes.