Banerjee S K, Banerjee S, Li S A, Li J J
University of Kansas Cancer Center, Department of Pharmacology, Kansas City.
Mutat Res. 1994 Dec 1;311(2):191-7. doi: 10.1016/0027-5107(94)90176-7.
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.
六十多年来，无论是天然雌激素还是合成雌激素，都被认为与包括人类在内的多种动物不同器官部位的致癌作用有关。然而，雌激素致癌作用所涉及的分子机制仍然存在争议且难以捉摸。在用强效或弱效雌激素进行不同时期的体内治疗后，对仓鼠肾脏的细胞遗传学损伤进行了研究。与年龄匹配的未处理对照组相比，己烯雌酚（DES）处理导致仓鼠肾皮质细胞中染色单体间隙和断裂、染色体断裂以及核内复制细胞的数量显著增加。随着激素持续暴露1.0至5.0个月，这些染色体畸变（CA）会累积。然而，由于断裂导致的染色体交换并未增加。在激素处理5.0个月后，强效雌激素如17β-雌二醇和莫昔芬在仓鼠肾脏中表现出与DES相似的CA频率，而弱效雌激素如17α-雌二醇和己二烯雌酚表现出的CA频率与未处理水平无显著差异。乙炔雌二醇在相似时期的处理导致染色单体间隙显著增加，尽管这些间隙并未发展为染色单体或染色体断裂的增加，同时核内复制细胞数量有所上升。这些结果增加了雌激素处理后产生的CA可能参与肾脏肿瘤发生过程的可能性。
