ELSEVIER Mutation Research 311 (1994) 191-197 Fundamental and Molecular Mechanisms of Mutagenesis Induction of chromosome aberrations in Syrian hamster renal cortical cells by various estrogens Sushanta K. Banerjee, Snigdha Banerjee, Sara Antonia Li, Jonathan J. Li * Hormonal Carcinogenesis Laboratory, Division of Etiology and Prevention of Hormonal Cancers, University of Kansas Cancer Center, Departments of Pharmacology, Toxicology, and Experimental Therapeutics, and Preventive Medicine, University of Kansas Medical Center, Robinson 5008, 3901 Rainbow Blvd., Kansas City, KS 66160-7417, USA Received 7 April 1994; revision received 5 June 1994;accepted 28 June 1994 Abstract Estrogens, both natural and synthetic, have been implicated in carcinogenesis at diffcrent 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 controls, 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 17fl-estradiol and Moxestrol exhibited similar frequencies of CA in the hamster kidney to that found for DES, whereas weak estrogens such as 17a-estradiol and/3-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. Keywords: Oestrogen induction; Chromosome aberrations; Hamster kidney; Tumorigenesis 1. Introduction Estrogens have been implicated in carcinogen- esis in numerous animals, including man (Li and Li, 1994a; Henderson et al., 1982). The molecular mechanism(s) involved in the carcinogenic action of estrogens remains both controversial and elu- * Corresponding author. sive. Recent evidence, however, from both in vivo and in vitro studies strongly suggests that estro- gens are epi-genotoxic carcinogens (Li and Li, 1994b; Li et al., 1993; Barrett et al., 1987); that is, they do not behave as direct acting mutagenic or DNA-damaging agents via covalent interaction with genetic material but instead elicit heritable changes by alternative mechanisms. The end re- sult is ultimately to cause heritable changes in the structure or sequence of the genetic material at 0027-5107/94/$07.00 © 1994 Elsevier Science B.V. All rights reserved SSDI 0027-5107(94)00133-2