Ames B N, Gold L S
Department of Molecular and Cell Biology, University of California, Berkeley 94720-3202, USA.
Biotherapy. 1998;11(2-3):205-20. doi: 10.1023/a:1007971204469.
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
认为滴滴涕等合成化学物质是人类癌症主要成因的观点,部分受到蕾切尔·卡森激情之作《寂静的春天》的启发。本章讨论了相关证据,说明为何事实并非如此。我们还回顾了癌症成因的研究,并展示了为何许多癌症是可预防的。流行病学证据表明,有几个因素可能对降低癌症发病率有重大影响: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在阳光下、增加体育活动、减少酒精消费以及可能减少红肉摄入。目前,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。如果排除主要由吸烟导致的肺癌,美国所有其他癌症合并后的死亡率正在下降。污染似乎在人类癌症中所占比例不到1%;然而,公众对化学污染的关注以及用于此的资源分配却非常高,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。在最大耐受剂量(MTD)下进行的动物癌症试验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,无论合成的还是天然的,在这些高剂量下对啮齿动物都是致癌的。阳性结果频率高的一个合理原因是,在最大耐受剂量下进行测试常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,而这种风险仅限于高剂量。忽视这一点会极大地夸大风险。科学家必须确定每种物质的致癌机制,并随着认识的进步修订可接受的剂量水平。人类摄入的绝大多数化学物质是天然的。例如,我们食用的农药中99.99%天然存在于植物中,用于抵御昆虫和其他捕食者。在最大耐受剂量下测试的这些天然农药中,有一半是啮齿动物致癌物。减少接触那0.01%的合成农药并不会降低癌症发病率。相反,尽管水果和蔬菜含有多种天然存在的化学物质,这些物质对啮齿动物是致癌物,但水果和蔬菜摄入不足会使大多数类型癌症的人类患病风险增加一倍。通过减少合成农药使用使其价格更贵会增加癌症风险。人类还会从烹饪食物中摄入大量天然化学物质。据报道,烘焙咖啡中有一千多种化学物质:其中超过一半(19/28)经过测试的是啮齿动物致癌物。一杯咖啡中的啮齿动物致癌物比普通美国人一年饮食中潜在致癌的农药残留还要多,而且烘焙咖啡中还有一千种化学物质有待测试。这并不意味着咖啡是危险的,而是说动物癌症试验和最坏情况风险评估内置了巨大的安全系数,不应被视为真实风险。人类能够食用种类繁多的天然化学“啮齿动物致癌物”的原因是,人类和其他动物一样,受到许多通用防御酶的极好保护,其中大多数是可诱导的(即每当一种防御酶在发挥作用时,就会产生更多)。由于防御酶对天然和合成化学物质同样有效,所以在高剂量啮齿动物试验中,人们既不期望也没有发现合成化学物质和天然化学物质在致癌能力上有普遍差异。认为人类癌症流行是由合成工业化学物质导致的观点是错误的。此外,发达国家的预期寿命在稳步上升。从啮齿动物的最大耐受剂量线性外推到人类的低水平接触导致了对死亡率的严重夸大预测。这样的外推……