文章：

化学物质引起的DNA损伤和人类癌症风险

Chemical-induced DNA damage and human cancer risk

原文发布日期：2004-08-01

DOI: 10.1038/nrc1410

类型: Review Article

开放获取: 否

要点：

1. More than 200 years after the first reports of chemically induced cancer in humans, many carcinogenic chemicals have been identified in the environment and the workplace.
2. Chemical carcinogenesis typically requires chronic exposure, followed by a period of years during which a complex series of events, involving DNA damage and alterations in gene expression, take place.
3. The earliest carcinogen-induced events typically include DNA structural damage, which often occurs as the result of covalent binding of carcinogens to DNA (DNA-adduct formation). This results in DNA mutations, leading to alterations in protein structure and function that can result in tumorigenesis.
4. In experimental models of chemical carcinogenesis, DNA adducts have been shown to be necessary, but not sufficient, for tumorigenesis. Proving such a relation in humans is difficult because it requires a correlation between DNA damage, which might have occurred 10–30 years earlier, and cancer incidence.
5. In recent years, progress has been made in our ability to detect carcinogen-induced DNA damage in humans. Two studies have shown that increases in DNA-adduct levels are associated with cancer risk in humans.
6. By analogy to experiments in animal models, administration of chemopreventive agents that reduce DNA-adduct formation might also reduce human cancer risk.
7. In regions of the world such as Linxian, China, where dietary exposure to polycyclic aromatic hydrocarbons is suspected in the aetiology of high oesophageal cancer rates and where reducing the level of this exposure is considered economically unfeasible, chemoprevention might be appropriate.

要点翻译：

1. 在人类首次报道化学物质诱发癌症的200多年后，环境和 workplace 中已有许多致癌化学物被确认。
2. 化学致癌作用通常需要长期暴露，随后经历数年时间，其间涉及DNA损伤和基因表达改变的一系列复杂事件相继发生。
3. 致癌物诱导的最早期事件通常包括DNA结构损伤，这常由致癌物与DNA共价结合（DNA加合物形成）所致。此类损伤引发DNA突变，导致蛋白质结构和功能改变，进而可能诱发肿瘤形成。
4. 在化学致癌作用的实验模型中，DNA加合物已被证明是肿瘤发生的必要条件而非充分条件。在人体中验证这种关系十分困难，因为需要将可能发生于10-30年前的DNA损伤与癌症发病率进行关联分析。
5. 近年来，人类检测致癌物诱导DNA损伤的能力取得进展。两项研究表明DNA加合物水平升高与人类癌症风险相关。
6. 类比动物模型实验，使用能减少DNA加合物形成的化学预防剂或可降低人类患癌风险。
7. 在中国林县等地区，膳食中多环芳烃暴露被怀疑是食管癌高发的重要病因，而降低该暴露水平在经济上被认为不可行，在此类地区实施化学预防可能具有适用价值。

英文摘要：

Chemical carcinogenesis involves a complex series of events, the earliest of which typically include DNA damage and the fixation of DNA mutations. Sophisticated new techniques have been developed to quantify DNA damage and to correlate the amount of damage with cancer risk. Approaches such as these are underway in Linxian, China, where food contains high levels of DNA-damaging, carcinogenic polycyclic aromatic hydrocarbons (PAHs), and where there is high mortality from oesophageal cancer. Gaining better insight into the mechanisms by which PAH exposure might increase oesophageal cancer risk could lead to new strategies for cancer prevention.

摘要翻译： 

化学致癌涉及一系列复杂事件，最早通常包括DNA损伤和DNA突变的固定。现已开发出先进的新技术来量化DNA损伤，并将损伤量与癌症风险相关联。在中国林县，这类研究正在进行，当地食物中含有高水平的DNA损伤性、致癌性多环芳烃（PAHs），且食管癌死亡率高。深入了解PAH暴露可能增加食管癌风险的机制，有望为癌症预防带来新策略。

原文链接：

Chemical-induced DNA damage and human cancer risk