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Mutagenicity of trans, trans‐muconaldehyde and its metabolites in V79 cells
Author(s) -
Chang R. L.,
Wong C. Q.,
Kline S. A.,
Conney A. H.,
Goldstein B. D.,
Witz G.
Publication year - 1994
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.2850240206
Subject(s) - metabolite , hypoxanthine guanine phosphoribosyltransferase , chemistry , chinese hamster , stereochemistry , genotoxicity , biochemistry , cis–trans isomerism , mutagen , microsome , alkylation , carcinogen , in vitro , toxicity , gene , organic chemistry , mutant , catalysis
Trans, trans‐Muconaldehyde (MUC), a six‐car‐bon‐diene‐dialdehyde, is a microsomal, hema‐totoxic ring‐opened metabolite of benzene. MUC is metabolized to a variety of compounds which are formed by oxidation and/or reduction of the aldehyde group(s). In the present studies, MUC and its metabolites were examined for mutagenic activity at the hypoxanthine guanine phosphoribosyltransferase (HGPRT) locus in Chinese hamster V79 cells. Mutagenicity was scored by counting 8‐azaguanine‐resistant colonies. Of the 6 compounds tested, MUC and its aldehydic metabolites 6‐hydroxy‐trans, trans 2, 4‐hexadienal and 6‐oxo‐trans, trans‐hexadi‐enoic acid were mutagenic in that order of potency. The other MUC metabolites tested (1, 6‐dihydroxy‐trans, trans‐2, 4‐hexadiene, trans, trans‐muconic acid, and 6‐hydroxy‐trans, trans‐2, 4‐hexadienoic acid) had little or no activity in this system. The order of mutagenic activity of MUC and its aldehydic metabolites correlates with their reactivity towards glutathione, suggesting that alkylating potential is important in the genotoxicity of these compounds. © 1994 Wiley‐Liss, Inc.