Effect of diet on aflatoxin B1-DNA binding and aflatoxin B1-induced glutathione S-transferase placental form positive hepatic foci in the rat.
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 mug/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.
Kimura
Masatomo
M
Fels Institute for Cancer Research and Molecular Biology, Department of Biochemistry, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Lehmann
Kiyoko
K
Gopalan-Kriczky
Prathima
P
Lotlikar
Prabhakar D
PD
D016604:Aflatoxin B1 / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D002471:Cell Transformation, Neoplastic; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004032:Diet; D005982:Glutathione Transferase / Q000032:analysis / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D008113:Liver Neoplasms / Q000209:etiology*; D008862:Microsomes, Liver / Q000201:enzymology; D051381:Rats
D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D016604:Aflatoxin B1; D005982:Glutathione Transferase