Journal Article

Effect of cell proliferation on initiation of aflatoxin B<sub>1</sub>-induced enzyme altered hepatic foci in rats and hamsters

Shingo Hiruma, Guo-Zhong Qin, Prathima Gopalan-Kriczky, Hisashi Shinozuka, Kiyomi Sato and Prabhakar D. Lotlikar

in Carcinogenesis

Volume 17, issue 11, pages 2495-2499
Published in print November 1996 | ISSN: 0143-3334
Published online November 1996 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/17.11.2495
Effect of cell proliferation on initiation of aflatoxin
                    B1-induced enzyme altered hepatic foci in rats and
                    hamsters

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Rat is susceptible whereas hamster is resistant to aflatoxin B1 (AFB1) hepatocarcinogenesis. Effect of cell proliferation on AFB1 -induced glutathione S-transferase placental form (GST-P) positive foci has been examined in these two species after a single i.p. dose of AFB1 and phenobarbital (PB) as a promoter in a 3 week period. Bromodeoxyuridine incorporation as a measure of cell proliferation and GST-P hepatic foci were analyzed by immunohistochemical methods. Hepatic cell proliferation was maximum at 24 h after either partial hepatectomy (PH) or CCl4 (4 mmol/ kg) pretreatment of rats whereas cell proliferation was maximum at 48 h after PH or CCl4 (1 mmol/kg) treatment of hamsters. Enhanced number of GST-P positive hepatic minifoci (two to nine cells) and foci (>100 μ) and focal area were observed in rats with either AFB1 (0.5 mg/kg) given 24 h after PH or AFB1 (0.5 or 2.5 mg/kg) given 48 h after CCl4 dosing. In hamsters, 1 or 2 mg AFB1 treatment produced only GST-P positive single hepatocytes without presence of any minifoci whereas 3 or 6 mg AFB1 produced minifoci consisting only of doublets. Pretreatment with CCl4 48 or 72 h before 1 mg AFB1 dose level increased GST-P positive single cells and minifoci several fold. PH 24 or 48 h before 1 or 2 mg AFB1 dose level increased minifoci. However, increase in minifoci was higher in PH hamsters at 48 h compared with those at 24 h. These results indicate that even though maximum initiation occurs in both speices when AFB1 is administered at the peak of DNA synthesis, rats are more responsive than hamsters to cellular proliferation in the initiation phase of AFB1 induced hepatocarcinogenesis.

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Subjects: Clinical Cytogenetics and Molecular Genetics

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