Effect of diet on aflatoxin B1-DNA binding and aflatoxin B1-induced glutathione S-transferase placental form positive hepatic foci in the rat.
- Author:
Masatomo KIMURA
1
;
Kiyoko LEHMANN
;
Prathima GOPALAN-KRICZKY
;
Prabhakar D LOTLIKAR
Author Information
1. Fels Institute for Cancer Research and Molecular Biology, Department of Biochemistry Temple University School of Medicine, Philadelphia, PA 19140, USA. lotlikar@temple.edu
- Publication Type:Original Article ; Research Support, U.S. Gov't, P.H.S.
- Keywords:
AFB1;
AFB1-DNA binding;
diet;
GST-P positive foci;
hepatocarcinogenesis
- MeSH:
Aflatoxin B1/metabolism/*pharmacology;
Animals;
Cell Transformation, Neoplastic;
Cytochrome P-450 Enzyme System/metabolism;
DNA/*metabolism;
*Diet;
Glutathione Transferase/analysis/*metabolism;
Hepatocytes/drug effects/*enzymology;
Liver Neoplasms/*etiology;
Microsomes, Liver/enzymology;
Rats;
Research Support, U.S. Gov't, P.H.S.
- From:Experimental & Molecular Medicine
2004;36(4):351-357
- CountryRepublic of Korea
- Language:English
-
Abstract:
Effects of diets on hepatic aflatoxin B1 (AFB1)- DNA binding and AFB1-induced glutathione S- transferase placental (GST-P) form positive hepatic foci have been examined in young male Fischer rats. Animals were fed either AIN-76A or Purina Chow (PC) diet for 1 wk before AFB1- DNA binding studies in vivo and in vitro. Animals 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 immunochemistry. Two h after i.p. injection of AFB1, hepatic AFB1-DNA binding in AIN-76A fed rats was twice as much as those in PC fed animals without affecting GSH levels. There was no significant effect of diet on either cytochrome P-450 content, GSH levels or microsomal 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 those in PC fed rats. The number of AFB1-induced GST-P positive foci was increased 5-10 fold in the presence of PB in both groups. In summary, 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.
