Effect of glucose administration on hamster liver S9-mediated mutagenesis, metabolism and DNA-binding of benzo[a]pyrene and aflatoxin B1.
Hamster liver S9 prepared from control animals and animals given 30% glucose in drinking water 48 h before killing was used in studies of benzo[a]pyrene (BaP) and aflatoxin (AFB1)-induced mutagenesis, metabolism of BaP and AFB1, and metabolite binding to calf thymus DNA. BAP-induced mutagenesis in Salmonella typhimurium TA100 was reduced 38.5% while AFB1-induced mutagenesis was increased 36% by S9 from glucose-treated hamsters. The reduction of [3H]BaP metabolite binding to calf thymus DNA in incubations with S9 from glucose-treated hamsters correlated with a decrease in unknown BP metabolite-deoxyribonucleoside adducts isolated by high performance liquid chromatography (HPLC). Differences in the 7R and 7S-diol epoxide-1 and 2 deoxyguanosine adducts of BaP between control and glucose-treated S9 were not observed. HPLC analysis of AFB1-DNA adducts showed a 25% increase in [3H]AFB1-N7-guanine in incubations of glucose-treated S9 with [3H]AFB1 and calf thymus DNA. HPLC analysis of the organosoluble fraction of incubations with [3H]BaP and [3H]AFB1 indicated a significant effect by glucose-treated S9 on metabolism. The effect of glucose on metabolism was further reflected in the reduction of both BaP and AFB1 metabolite conjugation with glucuronide and glutathione as determined by separation on an alumina column. These results indicate that the oral administration of 30% glucose in drinking water alters hamster liver S9-mediated mutagenesis and binding of BaP and AFB1 metabolites to DNA through an effect on the metabolism of these two carcinogens.
Rubano
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DC
Department of Physiology and Pharmacology, Loma Linda University School of Medicine, CA 92350.
Teel
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RW
Strother
A
A
D016604:Aflatoxin B1; D000348:Aflatoxins / Q000378:metabolism*; D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D006224:Cricetinae; D004247:DNA / Q000378:metabolism*; D004249:DNA Damage; D005947:Glucose / Q000494:pharmacology*; D005965:Glucuronates / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009154:Mutation; D013431:Sulfates / Q000378:metabolism
D000348:Aflatoxins; D005965:Glucuronates; D013431:Sulfates; D001564:Benzo(a)pyrene; D004247:DNA; D016604:Aflatoxin B1; D005978:Glutathione; D005947:Glucose