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Masatomo Kimura,Kiyoko Lehmann,Prathima Gopalan-Kriczky,Prabhakar D. Lotlikar 생화학분자생물학회 2004 Experimental and molecular medicine Vol.36 No.4
Efects of diets on hepatic aflatoxin B1 (AFB1)- DNA binding and AFB1-induced glutathione S- transferase placental (GST-P) form positive hepatic foci have ben examined in young male Fischer rats. Animals were fed either AIN-76A or 1- DNA binding studies in vivo and in vitro. Ani-mals were injected i.p. with AFB1 (1 mg/kg body wt) and 3 days later were given either AIN-76A or PC diet with or without 0.1% phenobarbital (PB) in their drinking water. All animals were sacrificed 10 wks after AFB1 dosing for analysis of AFB1-induced GST-P positive hepatic foci by imunochemistry. Two h after i.p. injection of AFB1, hepatic AFB1rats was twice as much as those in PC fed animals without affecting GSH levels. There was no significant effect of diet on either cyto-chrome P-450 content, GSH levels or micro-somal cytochrome P-450 mediated AFB1-DNA binding to exogenous DNA. There was a 40% increase in cytosolic GSH S-transferase activity with 1-chloro-2,4-dinitrobenzene as a substrate in PC fed animals compared to those given AIN- 76A diet. The number and area of AFB1-induced GST-P positive hepatic foci were twice and fivefold as much in AIN-76A fed compared to 1-indu-ced GST-P positive foci was increased 5-10 fold in the presence of PB in both groups. In sum-mary, the present data indicate that feeding of PC diet compared to AIN-76A diet inhibits the initiation phase whereas AIN-76A stimulates the promotion phase of AFB1 hepatocarcinogenesis in rats by inhibiting AFB1-DNA binding and increasing AFB1-induced hepatic foci respectively.
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