Klaunig James E, Kamendulis Lisa M
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Annu Rev Pharmacol Toxicol. 2004;44:239-67. doi: 10.1146/annurev.pharmtox.44.101802.121851.
Chemical carcinogenesis follows a multistep process involving both mutation and increased cell proliferation. Oxidative stress can occur through overproduction of reactive oxygen and nitrogen species through either endogenous or exogenous insults. Important to carcinogenesis, the unregulated or prolonged production of cellular oxidants has been linked to mutation (induced by oxidant-induced DNA damage), as well as modification of gene expression. In particular, signal transduction pathways, including AP-1 and NFkappaB, are known to be activated by reactive oxygen species, and they lead to the transcription of genes involved in cell growth regulatory pathways. This review examines the evidence of cellular oxidants' involvement in the carcinogenesis process, and focuses on the mechanisms for production, cellular damage produced, and the role of signaling cascades by reactive oxygen species.
化学致癌作用遵循一个涉及突变和细胞增殖增加的多步骤过程。氧化应激可通过内源性或外源性损伤导致活性氧和氮物种的过度产生而发生。对致癌作用至关重要的是，细胞氧化剂的不受调控或长期产生已与突变（由氧化剂诱导的DNA损伤引起）以及基因表达的改变有关。特别是，已知包括AP-1和NFκB在内的信号转导通路会被活性氧激活，并导致参与细胞生长调节通路的基因转录。本综述研究了细胞氧化剂参与致癌过程的证据，并重点关注其产生机制、所造成的细胞损伤以及活性氧信号级联反应的作用。
