Detection of carcinogen-induced stimulation of cytochrome P-448-associated enzymes by 14CO2 breath analysis studies using dimethylaminoazobenzene.
Rats pretreated with three agents known to stimulate cytochrome P-448-associated enzymes, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3-methylcholanthrene (3MC), and Aroclor 1254 were studied with a 14CO2 breath analysis technique after administration of [14C-dimethyl]aminoazobenzene (DMAB). The half-life of breath 14CO2 after [14C]DMAB administration was significantly decreased in the TCDD-, 3MC-, and Aroclor 1254-treated rats compared with controls. In vitro studies indicated that DMAB N-demethylase was increased by these three agents. Phenobarbital, an inducer of cytochrome P-450-associated enzymes, had no effect on 14CO2 half-life or on DMAB N-demethylase. Studies with [14C]aminopyrine, a cytochrome P-450 substrate, showed that TCDD and 3MC had no effect on 14CO2 half-life or aminopyrine N-demethylase; Aroclor 1254 and phenobarbital decreased 14CO2 half-life and stimulated aminopyrine N-demethylase. The data suggest that a [14C]DMAB breath analysis technique may be useful for in vivo studies of inducers of cytochrome P-448.
D000633:Aminopyrine N-Demethylase / Q000378:metabolism; D000818:Animals; D001140:Aroclors / Q000494:pharmacology*; D001944:Breath Tests; D002245:Carbon Dioxide / Q000032:analysis*; D002250:Carbon Radioisotopes; D003580:Cytochromes; D004146:Dioxanes / Q000494:pharmacology; D004147:Dioxins / Q000494:pharmacology*; D004790:Enzyme Induction; D005069:Evaluation Studies as Topic; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008722:Methods; D008748:Methylcholanthrene / Q000494:pharmacology*; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D051381:Rats; D004124:p-Dimethylaminoazobenzene
D001140:Aroclors; D002250:Carbon Radioisotopes; D003580:Cytochromes; D004146:Dioxanes; D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D002245:Carbon Dioxide; D008748:Methylcholanthrene; D004124:p-Dimethylaminoazobenzene; D011078:Polychlorinated Biphenyls; D010089:Oxidoreductases, N-Demethylating; D000633:Aminopyrine N-Demethylase; D010634:Phenobarbital