INCREASED YIELD IN GSP-P-POSITIVE LIVER PRENEOPLASTIC FOCI INDUCED BYDENA OR ENU IN RATS PRETREATED WITH ESTRADIOL OR TAMOXIFEN

We investigated the mechanisms by which partial hepatectomy (PH) incre ases the ability of chemical hepatocarcinogens to induce pre-neoplasti c liver foci. Comparison of the effects of pre-treatment with PH, estr adiol (E2) or tamoxifen (TAM) on the yield in glutathione-S-transferas e(GST-P)-positive pre-neoplastic foci in rat liver induced by subseque nt treatment with ethylnitrosourea (ENU) or diethylnitrosamine (DENA) showed that pre-treatment with E2 increased the yield in foci induced by subsequent treatment with ENU or DENA, as compared with that in ani mals not pre-treated, the increase being of similar magnitude with eit her carcinogen. Compared with that of PH, the effect of the hormone wa s much more pronounced than would be expected from the relative mitoge nic effect of the hormonal and surgical pre-treatments if the mitotic rate were the cause. On the other hand, the average volume of pre-neop lastic liver lesions in rats treated with ENU or DENA was 2.5 to 5.0 t imes higher than in rats not pre-treated whenever PH was included in t he pre-treatment, whereas it was not affected by any other pre-treatme nt. (C) 1993 Wiley-Liss, Inc.