The causes and prevention of cancer: the role of environment.

B N Ames, L S Gold
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引用次数: 97

Abstract

The idea that synthetic chemicals such as DDT are major contributors to human cancer has been inspired, in part, by Rachel Carson's passionate book, Silent Spring. This chapter discusses evidence showing why this is not true. We also review research on the causes of cancer, and show why much cancer is preventable. Epidemiological evidence indicates several factors 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 are avoidance of intense sun exposure, increases in physical activity, and reduction of alcohol consumption and possibly red meat. Already, risks of many forms of cancer can be reduced and the potential for further reductions is great. If lung cancer (which is primarily due to smoking) is excluded, cancer death rates are decreasing in the United States for all other cancers combined. Pollution appears to account for less than 1% of human cancer; yet public concern and resource allocation for chemical pollution are very high, in good part because of the use of animal cancer tests in cancer risk assessment. Animal cancer tests, which are done at the maximum tolerated dose (MTD), are being misinterpreted to mean that low doses of synthetic chemicals and industrial pollutants are relevant to human cancer. About half of the chemicals tested, whether synthetic or natural, are carcinogenic to rodents at these high doses. A plausible explanation for the high frequency of positive results is that testing at the MTD frequently can cause chronic cell killing and consequent cell replacement, a risk factor for cancer that can be limited to high doses. Ignoring this greatly exaggerates risks. Scientists must determine mechanisms of carcinogenesis for each substance and revise acceptable dose levels as understanding advances. The vast bulk of chemicals ingested by humans is natural. For example, 99.99% of the pesticides we eat are naturally present in plants to ward off insects and other predators. Half of these natural pesticides tested at the MTD are rodent carcinogens. Reducing exposure to the 0.01% that are synthetic will not reduce cancer rates. On the contrary, although fruits and vegetables contain a wide variety of naturally-occurring chemicals that are rodent carcinogens, inadequate consumption of fruits and vegetables doubles the human cancer risk for most types of cancer. Making them more expensive by reducing synthetic pesticide use will increase cancer. Humans also ingest large numbers of natural chemicals from cooking food. Over a thousand chemicals have been reported in roasted coffee: more than half of those tested (19/28) are rodent carcinogens. There are more rodent carcinogens in a single cup of coffee than potentially carcinogenic pesticide residues in the average American diet in a year, and there are still a thousand chemicals left to test in roasted coffee. This does not mean that coffee is dangerous but rather that animal cancer tests and worst-case risk assessment, build in enormous safety factors and should not be considered true risks. The reason humans can eat the tremendous variety of natural chemical "rodent carcinogens" is that humans, like other animals, are extremely well protected by many general defense enzymes, most of which are inducible (i.e., whenever a defense enzyme is in use, more of it is made). Since the defense enzymes are equally effective against natural and synthetic chemicals one does not expect, nor does one find, a general difference between synthetic and natural chemicals in ability to cause cancer in high-dose rodent tests. The idea that there is an epidemic of human cancer caused by synthetic industrial chemicals is false. In addition, there is a steady rise in life expectancy in the developed countries. Linear extrapolation from the maximum tolerated dose in rodents to low level exposure in humans has led to grossly exaggerated mortality forecasts. Such extrapo

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癌症的起因和预防:环境的作用。
认为滴滴涕等合成化学品是人类癌症的主要诱因的观点,部分是受到雷切尔·卡森充满激情的书《寂静的春天》的启发。本章讨论的证据表明,为什么这是不正确的。我们还回顾了有关癌症起因的研究,并说明了为什么许多癌症是可以预防的。流行病学证据表明,有几个因素可能对降低癌症发病率产生重大影响:减少吸烟、增加水果和蔬菜消费以及控制感染。其他因素包括避免强烈的阳光照射,增加体育活动,减少饮酒和可能的红肉。许多癌症的风险已经可以降低,而且进一步降低的潜力很大。如果将肺癌(主要由吸烟引起)排除在外,美国所有其他癌症的死亡率加起来都在下降。污染似乎占人类癌症的不到1%;然而,公众对化学污染的关注和资源分配非常高,这在很大程度上是因为在癌症风险评估中使用了动物癌症试验。以最大耐受剂量(MTD)进行的动物癌症试验被误解为意味着低剂量的合成化学品和工业污染物与人类癌症有关。在接受测试的化学物质中,无论是合成的还是天然的,在如此高的剂量下,大约有一半对啮齿动物是致癌的。对高频率阳性结果的合理解释是,在MTD频繁进行检测可能导致慢性细胞杀伤和随后的细胞替换,这是可限制在高剂量下的癌症风险因素。忽视这一点极大地夸大了风险。科学家必须确定每种物质的致癌机制,并随着了解的进展修改可接受的剂量水平。人类摄入的大部分化学物质都是天然的。例如,我们食用的99.99%的农药都是天然存在于植物中,用来抵御昆虫和其他捕食者。在MTD测试的这些天然农药中有一半是啮齿动物致癌物。减少接触0.01%的人工合成物质不会降低癌症发病率。相反,尽管水果和蔬菜含有多种自然产生的化学物质,这些化学物质是啮齿动物的致癌物,但水果和蔬菜的摄入不足会使人类患大多数癌症的风险增加一倍。通过减少合成农药的使用来提高它们的价格会增加癌症发病率。人类也会从烹饪食物中摄取大量的天然化学物质。据报道,烘焙咖啡中含有一千多种化学物质:其中一半以上(19/28)是啮齿动物致癌物。一杯咖啡中含有的啮齿动物致癌物比美国人一年平均饮食中潜在致癌的农药残留还要多,而且烘焙咖啡中还有上千种化学物质有待检测。这并不意味着咖啡是危险的,而是动物癌症测试和最坏情况风险评估,建立了巨大的安全因素,不应该被视为真正的风险。人类之所以能吃到种类繁多的天然化学“啮齿动物致癌物”,是因为人类和其他动物一样,受到许多一般防御酶的极好保护,其中大多数是可诱导的(即,只要使用一种防御酶,就会产生更多的防御酶)。由于防御酶对天然化学物质和合成化学物质同样有效,因此,在高剂量啮齿动物试验中,人们没有预料到,也没有发现,合成化学物质和天然化学物质在致癌能力方面存在普遍差异。人造工业化学品导致人类癌症流行的观点是错误的。此外,发达国家的预期寿命也在稳步上升。从啮齿动物的最大耐受剂量到人类的低水平暴露的线性外推导致了严重夸大的死亡率预测。这样extrapo
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