Application of the 32P-postlabelling assay to the inhibition of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-DNA adduct formation by dietary fatty acids.
The potent heterocyclic food mutagen IQ is carcinogenic in the CDF1 mouse, affecting the liver, lung and forestomach. Using 32P-postlabelling methods we have isolated up to five IQ-DNA adducts from both target and non-target organs after oral administration of IQ. Up to four additional non-specific adducts, found when the 32P-postlabelling assay was run under intensification conditions, could be attributed to the use of a certain brand of microcentrifuge tube in the assay. CLA is a mixture of heat-generated derivatives of linoleic acid, each with a conjugated double bond system, that has chemopreventive properties in rodents. To examine the effect of CLA on the formation of IQ-DNA adducts in CDF1 mice, we administered CLA by gavage every other day for 45 days, followed by a single oral dose (50 mg/kg) of IQ. Tissues collected 24 h later were analysed for IQ-DNA adducts by 32P-postlabelling. Compared to controls, CLA treatment caused inhibition of adduct formation in the liver, lung, large intestine and kidney. In the kidneys of females, CLA treatment inhibited IQ-DNA adduct formation almost completely (95.2%). Male F344 rats were fed a control diet or an isocaloric diet containing 20% menhaden oil (MO), a rich source of omega-3 fatty acids, for six weeks, then given a single oral dose of IQ. Analysis for IQ-DNA adducts by 32P-postlabelling one or six days later revealed that on day 1 the MO diet caused a 6-7 fold decrease in adduct formation in the liver and an up to 2-fold decrease in both the small and large intestine.(ABSTRACT TRUNCATED AT 250 WORDS)
Schut
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Department of Pathology, Medical College of Ohio, Toledo 43614.
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D000818:Animals; D004247:DNA / Q000187:drug effects* / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D009153:Mutagens / Q000378:metabolism* / Q000633:toxicity; D010761:Phosphorus Radioisotopes; D011804:Quinolines / Q000378:metabolism* / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D014018:Tissue Distribution
D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D009153:Mutagens; D010761:Phosphorus Radioisotopes; D011804:Quinolines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; D004247:DNA