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Single GST-P positive liver cells putative initiated. hepatocytes
1Department of Experimental Pathology, Cancer Institute Kami-Ikebukuro, Toshima-ku, Tokyo 170
2Department of Biochemistry, Hirosaki University School of Medicine Zaifu-cho, Hirosaki 036, Japan
3Present address:Carcinogenesis Research Unit, School of Pathology, University of NSW Kensington 2033, Australia
4To whom reprint requests should be sent
Immunohistochemical investigation of liver tissue 48 h after single doses of the hepatocarcinogens diethylnitrosamine (DEN), dimethylnitrosamine, aflatoxin B1 and methylazoxy-methanol acetate revealed the generation of a population of single glutathione S-transferase placental form (GST-P) positive hepatocytes. Yield was carcinogen dose dependent. Although the mixed function enzyme inducers sodium pheno barbital (PB), methyicholanthrene (Mech), polychlorinated biphenyls (PCB) and isosafrole (IS) did not in themselves induce comparable single cell lesions, their application prior to DEN caused significant alteration in the resultant numbers of GST-P positive hepatocytes observed. While PB and IS were associated with decreased yield, Mech and PCB, in con trast, brought about an increase. The results gained from investigation of the effects of 3-aminobenzamide adminis-tration and partial hepatectomy carried out at different times after carcinogen treatment also pointed to an initiated character for the lesions and suggest that GST-P may be a useful marker for analyzing factors relevant to the initiation stage of hepatocarcinogenesis. Thus the interplay between carcino-gen metabolism, DNA adduct formation and repair, toxicity and proliferation may be assessable in terms of numbers of enzyme-altered solitary hepatocytes.
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