Chang R L, Wong C Q, Kline S A, Conney A H, Goldstein B D, Witz G
Department of Chemical Biology and Pharmacognosy, College of Pharmacy, Rutgers.
Environ Mol Mutagen. 1994;24(2):112-5. doi: 10.1002/em.2850240206.
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 not 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.
反，反式粘康醛（MUC）是一种六碳二烯二醛，是苯的微粒体、血液毒性开环代谢产物。MUC可代谢为多种化合物，这些化合物通过醛基的氧化和/或还原形成。在本研究中，检测了MUC及其代谢产物在中国仓鼠V79细胞次黄嘌呤鸟嘌呤磷酸核糖转移酶（HGPRT）位点的致突变活性。通过计数抗8-氮杂鸟嘌呤菌落来评分致突变性。在所测试的6种化合物中，MUC及其醛代谢产物6-羟基反，反式-2,4-己二烯醛和6-氧代反，反式-己二烯酸按效力顺序具有致突变性。所测试的其他MUC代谢产物（1,6-二羟基反，反式-2,4-己二烯、反，反式粘康酸和6-羟基反，反式-2,4-己二烯酸）在该系统中几乎没有活性或没有活性。MUC及其醛代谢产物的致突变活性顺序与其对谷胱甘肽的反应性相关，这表明烷基化潜力在这些化合物的遗传毒性中很重要。
