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. 1993

H A Schut, and H X Zu
Department of Pathology, Medical College of Ohio, Toledo 43614.

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)

UI MeSH Term Description Entries
D008297 Male Males
D009153 Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. Clastogen,Clastogens,Genotoxin,Genotoxins,Mutagen
D010761 Phosphorus Radioisotopes Unstable isotopes of phosphorus that decay or disintegrate emitting radiation. P atoms with atomic weights 28-34 except 31 are radioactive phosphorus isotopes. Radioisotopes, Phosphorus
D011804 Quinolines
D011916 Rats, Inbred F344 An inbred strain of rat that is used for general BIOMEDICAL RESEARCH purposes. Fischer Rats,Rats, Inbred CDF,Rats, Inbred Fischer 344,Rats, F344,Rats, Inbred Fisher 344,CDF Rat, Inbred,CDF Rats, Inbred,F344 Rat,F344 Rat, Inbred,F344 Rats,F344 Rats, Inbred,Inbred CDF Rat,Inbred CDF Rats,Inbred F344 Rat,Inbred F344 Rats,Rat, F344,Rat, Inbred CDF,Rat, Inbred F344,Rats, Fischer
D004042 Dietary Fats, Unsaturated Unsaturated fats or oils used in foods or as a food. Dietary Oils,Unsaturated Dietary Fats,Dietary Fat, Unsaturated,Dietary Oil,Fat, Unsaturated Dietary,Fats, Unsaturated Dietary,Oil, Dietary,Oils, Dietary,Unsaturated Dietary Fat
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D004249 DNA Damage Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS. DNA Injury,DNA Lesion,DNA Lesions,Genotoxic Stress,Stress, Genotoxic,Injury, DNA,DNA Injuries
D004260 DNA Repair The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones. DNA Damage Response
D005227 Fatty Acids Organic, monobasic acids derived from hydrocarbons by the equivalent of oxidation of a methyl group to an alcohol, aldehyde, and then acid. Fatty acids are saturated and unsaturated (FATTY ACIDS, UNSATURATED). (Grant & Hackh's Chemical Dictionary, 5th ed) Aliphatic Acid,Esterified Fatty Acid,Fatty Acid,Fatty Acids, Esterified,Fatty Acids, Saturated,Saturated Fatty Acid,Aliphatic Acids,Acid, Aliphatic,Acid, Esterified Fatty,Acid, Saturated Fatty,Esterified Fatty Acids,Fatty Acid, Esterified,Fatty Acid, Saturated,Saturated Fatty Acids

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