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癌症的成因与预防:获取新视角。

The causes and prevention of cancer: gaining perspective.

作者信息

Ames B N, Gold L S

机构信息

Division of Biochemistry and Molecular Biology, University of California, Berkeley 94720-3202, USA.

出版信息

Environ Health Perspect. 1997 Jun;105 Suppl 4(Suppl 4):865-73. doi: 10.1289/ehp.97105s4865.

Abstract

Epidemiological studies have identified several factors that are likely to have a major effect on reducing rates of cancer: reduction of smoking, increased consumption of fruits and vegetables, and control of infections. Other factors include avoidance of intense sun exposure, increased physical activity, and reduced consumption of alcohol and possibly red meat. Risks of many types of cancer can already be reduced, and the potential for further reductions is great. In the United States, cancer death rates for all cancers combined are decreasing, if lung cancer (90% of which is due to smoking), is excluded from the analysis. We review the research on causes of cancer and show why much cancer is preventable. The idea that traces of synthetic chemicals, such as DDT, are major contributors to human cancer is not supported by the evidence, yet public concern and resource allocation for reduction of chemical pollution are very high, in part because standard risk assessment uses linear extrapolation from limited data in high-dose animal cancer tests. These tests are done at the maximum tolerated dose (MTD) and are typically misinterpreted to mean that low doses of synthetic chemicals and industrial pollutants are relevant to human cancer. About half the chemicals tested, whether synthetic or natural, are carcinogenic to rodents at such high doses. Almost all chemicals in the human diet are natural. For example, 99.99% of the pesticides we eat are naturally present in plants to ward off insects and other predators. Half of the natural pesticides that have been tested at the MTD are rodent carcinogens. Cooking food produces large numbers of natural dietary chemicals. Roasted coffee, for example, contains more than 1000 chemicals: of 27 tested, 19 are rodent carcinogens. Increasing evidence supports the idea that the high frequency of positive results in rodent bioassays is due to testing at the MTD, which frequently can cause chronic cell killing and consequent cell replacement-a risk factor for cancer that can be limited to high doses. Because default risk assessments use linear extrapolation, which ignores effects of the high dose itself, low-dose risks are often exaggerated.

摘要

流行病学研究已确定了几个可能对降低癌症发病率有重大影响的因素

减少吸烟、增加水果和蔬菜的摄入量以及控制感染。其他因素包括避免过度暴露于阳光下、增加体育活动、减少酒精摄入量以及可能减少红肉的摄入量。许多类型癌症的风险已经可以降低,而且进一步降低的潜力很大。在美国,如果将肺癌(其中90%归因于吸烟)排除在分析之外,所有癌症合并的癌症死亡率正在下降。我们回顾了关于癌症病因的研究,并说明为什么许多癌症是可以预防的。诸如滴滴涕等合成化学物质的微量痕迹是人类癌症的主要促成因素这一观点并未得到证据支持,但公众对减少化学污染的关注以及为此进行的资源分配却非常高,部分原因是标准风险评估使用高剂量动物癌症试验中的有限数据进行线性外推。这些试验是在最大耐受剂量(MTD)下进行的,通常被误解为意味着低剂量的合成化学物质和工业污染物与人类癌症有关。所测试的化学物质中,约一半无论是合成的还是天然的,在如此高的剂量下对啮齿动物都是致癌的。人类饮食中的几乎所有化学物质都是天然的。例如,我们摄入的农药中有99.99%天然存在于植物中,用于抵御昆虫和其他捕食者。在MTD下测试的天然农药中有一半是啮齿动物致癌物。烹饪食物会产生大量天然膳食化学物质。例如,烘焙咖啡含有1000多种化学物质:在测试的27种中,19种是啮齿动物致癌物。越来越多的证据支持这样一种观点,即啮齿动物生物测定中阳性结果的高频率是由于在MTD下进行测试,这经常会导致慢性细胞死亡以及随之而来的细胞替代——这是一种癌症风险因素,通常仅限于高剂量。由于默认风险评估使用线性外推,忽略了高剂量本身的影响,低剂量风险往往被夸大。

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