Modulation by estrogen of the incidence of diethylnitrosamine-induced gamma-glutamyltranspeptidase-positive foci in rat liver.

We measured the number and size of foci of altered hepatocytes induced after 8 weeks by diethylnitrosamine (DENA) in the liver of rats pretreated with 17 beta-estradiol (E2), 1 or 24 h prior to the administration of the carcinogen. The average size of the lesions was the same in the E2 pretreated and unpretreated animals. The number of gamma-glutamyltranspeptidase (GGT)-positive foci per cm3 of liver increased from 364 +/- 57 in unpretreated animals to 1149 +/- 186 in animals receiving E2 24 h before DENA; it raised to 3779 +/- 280 when the hormone was injected 1 h before the carcinogen, i.e. about 25% of the number of foci scored in rats receiving the carcinogen 24 h after partial hepatectomy. The hypothesis is proposed that 1-h pretreatment with E2 increases hepatocyte susceptibility towards DENA action by enhancing the accessibility of the genome to the carcinogen.