Increased yield in GST‐P‐positive liver pre‐neoplastic foci induced by dena or enu in rats pre‐treated with estradiol or tamoxifen

Abstract

We investigated the mechanisms by which partial hepatectomy (PH) increases the ability of chemical hepatocarcinogens to induce pre-neoplastic liver foci. Comparison of the effects of pre-treatment with PH, estradiol (E2) or tamoxifen (TAM) on the yield in glutathione-S-transferase(GST-P)-positive preneoplastic foci in rat liver induced by subsequent 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 animals not pre-treated, the increase being of similar magnitude with either carcinogen. Compared with that of PH, the effect of the hormone was much more pronounced than would be expected from the relative mitogenic effect of the hormonal and surgical pre-treatments if the mitotic rate were the cause. On the other hand, the average volume of pre-neoplastic liver lesions in rats treated with ENU or DENA was 2.5 to 5.0 times higher than in rats not pretreated whenever PH was included in the pre-treatment, whereas it was not affected by any other pre-treatment.