Correlation between induction of xenobiotic metabolism and DNA damage from chemical carcinogens in the chick embryo in vivo.
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.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D016604:Aflatoxin B1; D000348:Aflatoxins / Q000494:pharmacology; D000818:Animals; D002273:Carcinogens / Q000494:pharmacology*; D002642:Chick Embryo; D004247:DNA / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D004912:Erythrocytes / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000494:pharmacology; D013997:Time Factors
D000348:Aflatoxins; D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D004247:DNA; D016604:Aflatoxin B1; D008741:Methyl Methanesulfonate; D011078:Polychlorinated Biphenyls; D006899:Mixed Function Oxygenases; C028451:3,4,3',4'-tetrachlorobiphenyl; D010634:Phenobarbital