Eastmond D A
Environmental Toxicology Graduate Program, University of California, Riverside 92521-0127.
Toxicol Lett. 1993 Apr;67(1-3):105-18. doi: 10.1016/0378-4274(93)90049-4.
A number of carcinogens appear to exert their tumorigenic effects through the formation of quinone metabolites. These quinone-forming carcinogens are generally inactive or weakly active in standard gene mutation assays. Accumulating evidence indicates that this class of compounds may exert their genotoxic and carcinogenic effects through the induction of large-scale gene alterations. This article presents an overview of work that has been performed using recently developed molecular cytogenic techniques to investigate the aneuploidy-inducing and clastogenic properties of the major quinone-forming metabolites of benzene, a widely used industrial chemical, and o-phenylphenol, a fungicide and disinfectant. These metabolites of benzene (hydroquinone, catechol, and benzenetriol) and o-phenylphenol (phenylhydroquinone) have each been shown to be capable of interfering with chromosome segregation and inducing chromosomal breakage. These results indicate that both numerical and structural chromosomal aberrations induced by the quinone metabolites of benzene and o-phenylphenol may play a role in the carcinogenic effects of these two agents.
许多致癌物似乎通过形成醌类代谢产物发挥其致癌作用。这些形成醌的致癌物在标准基因突变试验中通常无活性或活性较弱。越来越多的证据表明,这类化合物可能通过诱导大规模基因改变发挥其遗传毒性和致癌作用。本文概述了利用最近开发的分子细胞遗传学技术开展的研究工作,这些研究旨在探究苯(一种广泛使用的工业化学品)和邻苯基苯酚(一种杀菌剂和消毒剂)主要形成醌的代谢产物的诱导非整倍体和致断裂特性。苯的这些代谢产物(对苯二酚、儿茶酚和苯三酚)以及邻苯基苯酚(苯基对苯二酚)均已被证明能够干扰染色体分离并诱导染色体断裂。这些结果表明,苯和邻苯基苯酚的醌类代谢产物诱导的染色体数目和结构畸变可能在这两种物质的致癌作用中发挥作用。