Organ specific modifying potential of ethinyl estradiol on carcinogenesis initiated with different carcinogens.
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 determine the effects of post-initiation phase administration of ethinyl estradiol (EE) on tumor development in the liver, kidney, lung, thyroid, bladder and esophagus of male F344 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-acetylaminofluorene (2-AAF) or 0.05% N-butyl-N-(4-hydroxybutyl)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-initiated group but an opposite increase in the NPD-initiated animals. No effect of EE was evident regarding thyroid lesions.
D015073:2-Acetylaminofluorene; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D004052:Diethylnitrosamine / Q000031:analogs & derivatives; D004347:Drug Interactions; D004938:Esophageal Neoplasms / Q000139:chemically induced; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D007680:Kidney Neoplasms / Q000139:chemically induced; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008175:Lung Neoplasms / Q000139:chemically induced; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009602:Nitrosamines; D051381:Rats; D011916:Rats, Inbred F344; D013964:Thyroid Neoplasms / Q000139:chemically induced; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced
D007527:Isoenzymes; D009602:Nitrosamines; C023845:N-ethyl-N-hydroxyethylnitrosamine; D004052:Diethylnitrosamine; D004997:Ethinyl Estradiol; C012457:diisopropanolnitrosamine; C002743:N-nitrosopiperidine; D015073:2-Acetylaminofluorene; D005982:Glutathione Transferase