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

被引:13
作者
CHANG, RL
WONG, CQ
KLINE, SA
CONNEY, AH
GOLDSTEIN, BD
WITZ, G
机构
[1] RUTGERS STATE UNIV,COLL PHARM,DEPT CHEM BIOL & PHARMACOGNOSY,CANC RES LAB,PISCATAWAY,NJ 08855
[2] UNIV MED & DENT NEW JERSEY,ROBERT WOOD JOHNSON MED SCH,DEPT ENVIRONM & COMMUNITY MED,PISCATAWAY,NJ 08854
关键词
RING-OPENED BENZENE METABOLITES; HGPRT MUTATIONS; MUCONALDEHYDE;
D O I
10.1002/em.2850240206
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
trans,trans-Muconaldehyde (MUC), a six-carbon-diene-dialdehyde, is a microsomal, hematotoxic 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-hexadienoic 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. (C) 1994 Wiley-Liss, Inc.
引用
收藏
页码:112 / 115
页数:4
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