Initiation of focal hyperplastic hepatic lesions by transplacental administration of ethylnitrosourea in rats of F1 generation, and no transmission of the effect to F2 and F3 generations.

Abstract

Administration of ethylnitrosourea (ENU) to pregnant rats in the late stage of gestation has been known to have a mainly neurocarcinogenic action on the progeny. However, when transplacental administration of ENU was combined in postnatal life with a brief dietary exposure to 2-acetylaminofluorene (2-AAF) and a two-thirds partial hepatectomy, numerous focal hyperplastic lesions of gamma-glutamyltranspeptidase (GGT)-positive hepatocytes emerged in the liver of the progeny. On the other hand, rats of F2 generation born of F1 parents and F3 rats born of F2 parents showed no increase in the incidence of hepatic lesions after treatment with the same dietary regimen. It was suggested that direct interaction between fetal liver cells and the carcinogen is important for occurrence of initiated hepatocytes and that the initiation effect on rat liver by ENU does not persist in the descendants of F2 and F3 generations.