Detection of carcinogen-induced stimulation of cytochrome P-448-associated enzymes by 14CO2 breath analysis studies using dimethylaminoazobenzene

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 76; no. 2; p. 267
• Main Authors: Hepner, G W, Piken, E P
• Format: Journal Article
• Language: English
• Published: United States 01.02.1979
• Subjects: Aminopyrine N-Demethylase - metabolism; Animals; Aroclors - pharmacology; Breath Tests; Carbon Dioxide - analysis; Carbon Radioisotopes; Cytochromes; Dioxanes - pharmacology; Dioxins - pharmacology; Enzyme Induction; Evaluation Studies as Topic; Liver - drug effects; Liver - enzymology; Male; Methods; Methylcholanthrene - pharmacology; Oxidoreductases, N-Demethylating - metabolism; p-Dimethylaminoazobenzene; Phenobarbital - pharmacology; Polychlorinated Biphenyls - pharmacology; Polychlorinated Dibenzodioxins - pharmacology; Rats
• ISSN: 0016-5085
• DOI: 10.1016/0016-5085(79)90332-9

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.