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Correlation between induction of xenobiotic metabolism and DNA damage from chemical carcinogens in the chick embryo in vivo. 1986

J W Hamilton, and S E Bloom

Chick embryo liver and lung have high levels of basal mixed-function oxidase (MFO) enzyme activities during embryonic development. These activities are differentially inducible by 3,4,3',4'-tetrachlorobiphenyl (TCB) and phenobarbital (PB) in liver but are not inducible in lung. Nucleated chick embryo erythrocytes have no detectable basal or inducible MFO activities. Following induction by TCB or PB, embryos were exposed to the direct-acting carcinogen methyl methane-sulfonate (MMS) or the indirect-acting carcinogens aflatoxin B1 (AFB1) or 7,12-dimethylbenz[a]anthracene (DMBA). DNA damage was measured in liver, lung and blood by the DNA alkaline elution technique. Maximum DNA damage by MMS in liver, lung and blood and by AFB1 and DMBA in liver and lung occurred approximately 3 h after exposure. DNA damage was rapidly repaired in liver and lung, but was not repaired in blood. AFB1 and DMBA caused no detectable DNA damage in blood, even following PB or TCB induction. MMS-induced DNA damage was unaffected by induction in all groups with the exception that PB decreased DNA damage in liver at the low dose of MMS. AFB1- and DMBA-induced DNA damage was increased in liver and decreased in lung following induction by PB and TCB in 14-day embryos. In contrast, AFB1-induced DNA damage was increased by PB and decreased by TCB in 7-day embryonic liver. These results suggest that MFO induction can increase or decrease DNA damage in vivo, but that the direction and magnitude of change in DNA damage can vary depending on the inducer, carcinogen, tissue and the developmental age being investigated.

UI MeSH Term Description Entries
D008099 Liver A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances. Livers
D008168 Lung Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood. Lungs
D008741 Methyl Methanesulfonate An alkylating agent in cancer therapy that may also act as a mutagen by interfering with and causing damage to DNA. Methylmethane Sulfonate,Dimethylsulfonate,Mesilate, Methyl,Methyl Mesylate,Methyl Methylenesulfonate,Methylmesilate,Mesylate, Methyl,Methanesulfonate, Methyl,Methyl Mesilate
D010634 Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D011078 Polychlorinated Biphenyls Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants. PCBs,Polychlorinated Biphenyl,Polychlorobiphenyl Compounds,Biphenyl, Polychlorinated,Biphenyls, Polychlorinated,Compounds, Polychlorobiphenyl
D002273 Carcinogens Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included. Carcinogen,Oncogen,Oncogens,Tumor Initiator,Tumor Initiators,Tumor Promoter,Tumor Promoters,Initiator, Tumor,Initiators, Tumor,Promoter, Tumor,Promoters, Tumor
D002642 Chick Embryo The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching. Embryo, Chick,Chick Embryos,Embryos, Chick
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
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme

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