Detection of carcinogen-induced stimulation of cytochrome P-448-associated enzymes by /sup 14/CO/sub 2/ 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 /sup 14/CO/sub 2/ breath analysis techniqe after administration of /sup 14/C-dimethyl aminoazobenzene (DMAB). The half-life of breath /sup 14/CO2 after (/sup 14/C)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 /sup 14/CO/sub 2/ half-life or on DMAB N-demethylase. Studies with (/sup 14/C)aminopyrine, a cytochrome P-450 substrate, showed that TCDD and 3MC had no effect on /sup 14/CO/sub 2/ half-life or aminopyrine N-demethylase; Aroclor 1254 and phenobarbital decreased /sup 14/CO/sub 2/ half-life and stimulated aminopyrine N-demethylase. The data suggest that a (/sup 14/C)DMAB breath analysis technique may be useful for in vivo studies of inducers of cytochrome P-448.
- Research Organization:
- Harbor/UCLA Medical Center, Torrance, CA
- OSTI ID:
- 5586759
- Journal Information:
- Gastroenterology; (United States), Journal Name: Gastroenterology; (United States) Vol. 76:2; ISSN GASTA
- Country of Publication:
- United States
- Language:
- English
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62 RADIOLOGY AND NUCLEAR MEDICINE
ALKYL RADICALS
AMINES
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AROMATICS
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