多氯联苯作为肝细胞癌的起始剂。
Polychlorinated biphenyls (PCBs) as initiating agents in hepatocellular carcinoma.
作者信息
Ludewig Gabriele, Robertson Larry W
机构信息
The University of Iowa, 100 Oakdale Campus, IREH, Iowa City, IA 52242-5000, United States.
The University of Iowa, 100 Oakdale Campus, IREH, Iowa City, IA 52242-5000, United States.
出版信息
Cancer Lett. 2013 Jun 28;334(1):46-55. doi: 10.1016/j.canlet.2012.11.041. Epub 2012 Dec 2.
Abstract
PCBs are carcinogens, but for many decades it was assumed that PCBs may not possess initiating activity. Initiation is a process that involves changes in the DNA sequence, often, but not exclusively produced through DNA adduction by a reactive compound or reactive oxygen species (ROS). DNA adducts can be detected by (32)P-postlabeling, a method that Dr. Ramesh Gupta co-developed and refined. Today these types of assays together with other mechanistic studies provide convincing evidence that specific PCB congeners can be biotransformed to genotoxic and therefore potentially initiating metabolites. This review will provide an overview of our current knowledge of PCBs' genotoxic potential and mechanism of action, emphasizing the contributions of Dr. Ramesh Gupta during his tenures at the Universities of Kentucky and Louisville.
摘要
多氯联苯是致癌物，但几十年来人们一直认为多氯联苯可能不具有引发活性。引发是一个涉及DNA序列变化的过程，通常但并非仅仅由反应性化合物或活性氧（ROS）与DNA加合产生。DNA加合物可以通过（32）P后标记法检测，拉梅什·古普塔博士共同开发并完善了该方法。如今，这类检测方法以及其他机理研究提供了令人信服的证据，表明特定的多氯联苯同系物可生物转化为具有基因毒性的、因此可能具有引发作用的代谢物。本综述将概述我们目前对多氯联苯基因毒性潜力及其作用机制的认识，重点介绍拉梅什·古普塔博士在肯塔基大学和路易斯维尔大学任职期间所做的贡献。
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