The in utero 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 (and fetal) primary rat hepatocytes (i) immunocytochemically detectable, widespread increases in their complement of the alpha, mu and especially pi classes of cytosolic glutathione S-transferases (GSTs); and (ii) changed patterns (with respect to controls) of the phenobarbital (PB)-evoked increases in steady state levels of c-jun and c-myc mRNA's. These results indicate that DMN causes both transient cytotoxic effects and a broad, permanent initiation in fetal proliferating hepatocytes.
Armato
U
U
Institute of Anatomy, School of Medicine, University of Verona, Italy.
Wu
J
J
Menegazzi
M
M
Menapace
L
L
Ribecco
M
M
Testolin
L
L
Carcereri De Prati
A
A
Suzuki
H
H
D000818:Animals; D000831:Animals, Newborn; D001709:Biotechnology; D002478:Cells, Cultured; D004128:Dimethylnitrosamine / Q000633:toxicity*; D005260:Female; D016758:Genes, jun / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D008431:Maternal-Fetal Exchange; D010634:Phenobarbital / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats
D005982:Glutathione Transferase; D004128:Dimethylnitrosamine; D010634:Phenobarbital