Organ specific modifying potential of ethinyl estradiol on carcinogenesis initiated with different carcinogens

Estrogen has been shown to exert a modifying potential on carcinogenesisin various organs, and in particular the hormone-dependent tissues.The present experiments were carried out to detennine the effectsof post-initiation phase administration of etbinyl estradiol(EE) on tumor development in the liver, kidney, lung, thyroid,bladder and esophagus of male E344 rats. Animals were initiatedby 2 weeks treatment with 0.05% N-bis(2-hydroxypropyl)nitrosamine(DHPN), 0.1% N-ethyl-N-hydroxyethylnitrosamine (EHEN), 0.03%N-nitrosopiperidine (NPD), 0.02% 2-acetyl-aminofluorene (2-AAF)or 0.05% N-butyl-N-(4-hydroxy-butyl)nitrosamine (BBN) in theirdiet or drinking water, and starting 1 week after initiation,they were given diet with or without a 0.001% EE supplementfor 49 weeks, at which point the experiment was terminated.EE significantly increased the development of tumors of theliver (DHPN-, EHEN-, 2-AAF-and NPD-treated groups) and kidneys(EHEN-treated group) but inhibited their development in thelungs (DHPN treated group) and urinary bladder (BBN-treatedgroup). In the liver, EE also increased the development of glutathioneS-transferase P type-positive lesions to various extents dependingon the initiator used. EE administration was associated witha decreased incidence of esophageal hyperplasia in the EHEN-initlatedgroup but an opposite increase in the NPD initiated animals.No effect of EE was evident regarding thyroid lesions.