THE INUTERO INITIATION WITH DMN ALTERS THE COMPLEMENT OF CYTOSOLIC GLUTATHIONE S-TRANSFERASES AND THE PHENOBARBITAL-INDUCED EXPRESSION OF C-JUN AND C-MYC ONCOGENES IN PRIMARY NEONATAL RAT HEPATOCYTES

As revealed by a novel in utero-in vitro hepatocarcinogenesis model, a single exposure to dimethylnitrosamine (DMN) elicited in postnatal (a nd fetal) primary rat hepatocytes (i) immunocytochemically detectable, widespread increases in their complement of the alpha, mu and especia lly pi classes of cytosolic glutathione S-transferases (GSTs); and (ii ) changed patterns (with respect to controls) of the phenobarbital (PB )-evoked increase in steady state levels of c-jun and c-myc mRNA's. Th ese results indicate that DMN causes both transient cytotoxic effects and a broad, permanent initiation in fetal proliferating hepatocytes.