MUTAGENICITY OF TRANS,TRANS-MUCONALDEHYDE AND ITS METABOLITES IN V79 CELLS

trans,trans-Muconaldehyde (MUC), a six-carbon-diene-dialdehyde, is a m icrosomal, hematotoxic ring-opened metabolite of benzene. MUC is metab olized to a variety of compounds which are formed by oxidation and/or reduction of the aldehyde group(s). In the present studies, MUC and it s metabolites were examined for mutagenic activity at the hypoxanthine guanine phosphoribosyltransferase (HGPRT) locus in Chinese hamster V7 9 cells. Mutagenicity was scored by counting 8-azaguanine-resistant co lonies. Of the 6 compounds tested, MUC and its aldehydic metabolites 6 -hydroxy-trans,trans-2,4-hexadienal and 6-oxo-trans,trans-hexadienoic acid were mutagenic in that order of potency. The other MUC metabolite s tested (1,6-dihydroxy-trans, trans-2, 4-hexadiene, trans, trans-muco nic 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. (C) 1994 Wiley-Liss, Inc.