Thein utero initiation with DMN alters the complement of cytosolic glutathione S-transferases and the phenobarbital-induced expression ofc-jun andc-myc oncogenes in primary neonatal rat hepatocytes

As revealed by a novelin utero-in vitro hepatocarcinogenesis model, a single exposure to dimethylnitrosamine (DMN) elicited in postnatal (and fetal) primary rat hepatocytes (i) immunocytochemically detectable, widespread increases in their complement of thealpha, mu and especiallypi classes of cytosolic glutathione S-transferases (GST's); and (ii) changed patterns (with respect to controls) of the phenobarbital (PB)-evoked increases in steady state levels ofc-jun andc-myc mRNA's. These results indicate that DMN causes both transient cytotoxic effects and a broad, permanent initiation in fetal proliferating hepatocytes.