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

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Abstract
Estrogen has been shown to exert a modifying potential on carcinogenesis in various organs, and in particular the hormone-dependent tissues. The present experiments were carried out to detennine the effects of 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 initiated by 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 their diet or drinking water, and starting 1 week after initiation, they were given diet with or without a 0.001% EE supplement for 49 weeks, at which point the experiment was terminated. EE significantly increased the development of tumors of the liver (DHPN-, EHEN-, 2-AAF-and NPD-treated groups) and kidneys (EHEN-treated group) but inhibited their development in the lungs (DHPN treated group) and urinary bladder (BBN-treated group). In the liver, EE also increased the development of glutathione S-transferase P type-positive lesions to various extents depending on the initiator used. EE administration was associated with a decreased incidence of esophageal hyperplasia in the EHEN-initlated group but an opposite increase in the NPD initiated animals. No effect of EE was evident regarding thyroid lesions.