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KMID : 0620919960280030135
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Experimental & Molecular Medicine
1996 Volume.28 No. 3 p.135 ~ p.140
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A mechanism of inhibition of aflatoxin B1 hepatocarcinogenesis by β-naphthoflavone pretreatment of rats
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K. Santhanam
Lingling Ho
Prathima Gopalan-Kriczky
Prabhakar D. Lotlikar
Lingling Ho
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Abstract
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Pretreatment with β-naphthoflavone (BNF) inhibits aflatoxin B1 (AFB1) hepatocarcinogenesis in the rat by stimulation of aflatoxin M1 (AFM1) hydroxylation. We have now examined the effect of BNF pretreatment of rats on AFB1-hydroxylations, AFB1- DNA binding and AFB1-glutathione (AFB1-SG) conjugation in liver in vitro, in vivo and in isolated hepatocytes. Male Fischer rats were injected i.p. with either corn oil or BNF (25 mg/kg body weight) 24 h before for in vitro and in isolated hepatocyte studies. Cytochrome P-450 contents in BNF-treated rat liver microsomes and hepatocytes were 170% and 200% of controls, respectively. At two AFB1- concentrations (2 μM and 100 μM), AFB1- epoxidation measured as AFB1-DNA binding and AFM1 hydroxylation were 60% and 300% of controls, respectively. At low AFBl level (33 nM), AFB1-binding and AFM1 formation in BNF-treated hepatocytes were 40% and 225% of controls, respectively. Formation of AFB1-SG, aflatoxin Q1 and aflatoxin P1 were not affected significantly. Hepatic nuclear AFB1-DNA binding 2 h after i.p. injection of 0.4 mg [3H]AFB1/kg body wt. in BNF-treated rats was 60% of controls. The overall data indicate that lower AFB1-DNA binding in addition to higher inactivation via AFM1 hydroxylation are responsible for the inhibition of AFB1 hepato- carcinogenesis by BNF pretreatment of rats. It is suggested that this inhibition of AFB1-DNA binding may be a direct result of lower levels of constitutive cytochromes P-450 responsible for AFB1-epoxidation.
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KEYWORD
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aflatoxin B₁-DNA binding, AFB₁-epoxide, aflatoxin M₁hydroxylation, β-naphthoflavone
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