2-(4'-氯苯基)-1,4-苯醌增加微核频率并缩短端粒。
2-(4'-CHLOROPHENYL)-1,4-BENZOQUINONE INCREASES THE FREQUENCY OF MICRONUCLEI AND SHORTENS TELOMERES.
作者信息
Jacobus J A, Flor S, Klingelhutz A, Robertson L W, Ludewig G
机构信息
Department of Occupational and Environmental Health, University of Iowa, 100 Oakdale Campus # 124 IREH, Iowa City, IA 52242-5000.
出版信息
Environ Toxicol Pharmacol. 2008 Mar;25(2):267-272. doi: 10.1016/j.etap.2007.10.022.
Abstract
The toxicity of polychlorinated biphenyls (PCBs) has been attributed widely to receptor-mediated effects, buttressed by the popularity of the Toxic Equivalency Factor. We propose that a crucial toxic mechanism of lower-chlorinated PCBs is their enzymatic biotransformation to electrophiles, including quinoid metabolites, that bind intracellular sulfhydryl groups, such as those found in microtubulin and enzymes like telomerase. To test this hypothesis, we have examined micronuclei induction, cell cycle, and telomere shortening in cells in culture. Our findings show a large increase in micronuclei frequency and cell cycle perturbation in V79 cells, and a marked decrease in telomere length in HaCaT cells exposed to 2-(4'-chlorophenyl)-1,4-benzoquinone (PCB3pQ).
摘要
多氯联苯（PCBs）的毒性广泛归因于受体介导的效应，这一观点因毒性当量因子的广泛应用而得到支持。我们提出，低氯代多氯联苯的一个关键毒性机制是它们经酶促生物转化为亲电试剂，包括醌类代谢产物，这些亲电试剂会与细胞内的巯基结合，如微管蛋白和端粒酶等酶中的巯基。为了验证这一假设，我们检测了培养细胞中的微核诱导、细胞周期和端粒缩短情况。我们的研究结果表明，暴露于2-(4'-氯苯基)-1,4-苯醌（PCB3pQ）的V79细胞中微核频率大幅增加且细胞周期受到干扰，而HaCaT细胞中的端粒长度显著缩短。
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