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.
Taton
G
G
Laboratory of Cytology and Experimental Cancerology, School of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
Servais
P
P
Galand
P
P
D000818:Animals; D004052:Diethylnitrosamine / Q000633:toxicity; D004790:Enzyme Induction / Q000187:drug effects; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D008099:Liver / Q000201:enzymology*; D011230:Precancerous Conditions / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013047:Specific Pathogen-Free Organisms; D005723:gamma-Glutamyltransferase / Q000096:biosynthesis*
D004967:Estrogens; D004052:Diethylnitrosamine; D005723:gamma-Glutamyltransferase