School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston PR1 2HE, U.K.
Carcinogen-DNA Interactions Section, LCBG, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, MD 20892-4255, U.S.A.
Biochem Soc Trans. 2018 Oct 19;46(5):1213-1224. doi: 10.1042/BST20180519. Epub 2018 Oct 3.
Humans are variously and continuously exposed to a wide range of different DNA-damaging agents, some of which are classed as carcinogens. DNA damage can arise from exposure to exogenous agents, but damage from endogenous processes is probably far more prevalent. That said, epidemiological studies of migrant populations from regions of low cancer risk to high cancer risk countries point to a role for environmental and/or lifestyle factors playing a pivotal part in cancer aetiology. One might reasonably surmise from this that carcinogens found in our environment or diet are culpable. Exposure to carcinogens is associated with various forms of DNA damage such as single-stand breaks, double-strand breaks, covalently bound chemical DNA adducts, oxidative-induced lesions and DNA-DNA or DNA-protein cross-links. This review predominantly concentrates on DNA damage induced by the following carcinogens: polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, mycotoxins, ultraviolet light, ionising radiation, aristolochic acid, nitrosamines and particulate matter. Additionally, we allude to some of the cancer types where there is molecular epidemiological evidence that these agents are aetiological risk factors. The complex role that carcinogens play in the pathophysiology of cancer development remains obscure, but DNA damage remains pivotal to this process.
人类会持续不断地接触到各种各样的不同 DNA 损伤剂,其中有些被归为致癌物。DNA 损伤可能来自于外源性物质的暴露,但内源性过程造成的损伤可能更为常见。话虽如此,来自癌症低发地区的移民人群的流行病学研究表明,环境和/或生活方式因素在癌症发病机制中起着关键作用。由此人们可能合理地推断,我们环境或饮食中的致癌物是罪魁祸首。致癌物的暴露与多种形式的 DNA 损伤有关,如单链断裂、双链断裂、共价结合的化学 DNA 加合物、氧化诱导损伤以及 DNA-DNA 或 DNA-蛋白质交联。这篇综述主要集中在以下致癌物引起的 DNA 损伤:多环芳烃、杂环芳香胺、霉菌毒素、紫外线、电离辐射、马兜铃酸、亚硝胺和颗粒物。此外,我们还提到了一些癌症类型,有分子流行病学证据表明这些物质是病因风险因素。致癌物在癌症发展的病理生理学中所扮演的复杂角色仍不清楚,但 DNA 损伤在这一过程中仍然至关重要。