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HERO ID
625962
Reference Type
Journal Article
Title
In vitro system for detecting nongenotoxic carcinogens
Author(s)
Dertinger, SD; Torous, DK; Tometsko, AM
Year
1993
Is Peer Reviewed?
Yes
Journal
Environmental and Molecular Mutagenesis
ISSN:
0893-6692
EISSN:
1098-2280
Report Number
EMIC/90849
Volume
21
Issue
4
Page Numbers
332-338
Language
English
PMID
8491212
DOI
10.1002/em.2850210404
Abstract
Chemical risk assessment has been limited by the inability of in vitro short-term assays to identify the true carcinogenic potential of many substances. Numerous methods exist for identifying mutagenic and clastogenic agents, but a practical means of identifying nongenotoxic carcinogens has remained elusive. Experiments described here suggest that some chemicals may participate in carcinogenesis by modulating the enzymatic processes of drug metabolism. The tumor promoters butylated hydroxyanisole, butylated hydroxytoluene, deoxycholic acid, reserpine, trypan blue, and 12,-O-tetradecanoyl phorbol-13-acetate were chosen as model non-genotoxic carcinogens. The enzyme-modulating action of these chemicals was measured using a modified Ames plate incorporation assay whereby the known tumor promoters were plated with a promutagen in the presence of a mammalian metabolic activation system (S9). Each of the nongenotoxic carcinogens significantly increased the mutagenic response of metabolically activated promutagen(s). These experiments suggest that the carcinogenic role of some chemicals may be attributed to their ability to modify the biochemical pathways of drug metabolism. By enhancing or inhibiting the activity of various enzymes, some tumor promoters may create an environment that increases a cell's mutational burden, thereby contributing to neoplastic transformation.
Keywords
carcinogenic risk; tumor promotion; Salmonella typhimurium; Ames test; metabolic activation
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