ENDOGENOUS MUTAGENS AND THE CAUSES OF AGING AND CANCER
ENDOGENOUS MUTAGENS AND THE CAUSES OF AGING AND CANCER
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DOI：
10.1016/0027-5107(91)90157-j
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发表时间：
1991-09-01
期刊：
影响因子：
--
通讯作者：
GOLD, LS
中科院分区：
文献类型：
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作者：
AMES, BN;GOLD, LS
作为正常代谢的一部分，DNA的氧化损伤率非常高。在每个大鼠细胞中，估计稳态水平约为10(6)个氧化加合物，并且每天约形成10(5)个新加合物。有人认为，这种内源性DNA损伤是衰老和衰老引起的退行性疾病（如癌症）的主要原因。代谢率高、寿命短、年龄特异性癌症发病率高的哺乳动物的氧化损伤率远高于人类，而人类是寿命长、代谢率低、年龄特异性癌症发病率低的动物。有人认为，缺乏微量营养素，如膳食抗氧化剂或叶酸，是人类癌症和退行性疾病的主要原因。了解有丝分裂发生在突变中的作用对于阐明癌变机制和解释高剂量动物癌症试验至关重要。高剂量动物癌症试验主要是在合成工业化学品上进行的，然而人类接触到的几乎所有化学品都是天然的。在高剂量动物癌症试验中，大约一半的天然化学物质是啮齿动物致癌物，这一发现与高剂量试验经常增加有丝分裂率的观点相一致。动物对毒素有许多防御能力，这使它们对几乎所有低剂量的毒素都有很好的缓冲，无论是合成的还是天然的。
A very large oxidative damage rate to DNA occurs as part of normal metabolism. In each rat cell the steady-state level is estimated to be about 10(6) oxidative adducts and about 10(5) new adducts are formed daily. It is argued that this endogenous DNA damage is a major contributor to aging and the degenerative diseases of aging, such as cancer. The oxidative damage rate in mammalian species with a high metabolic rate, short life span, and high age-specific cancer rate is much higher than the rate in humans, a long-lived creature with a lower metabolic rate and a lower age-specific cancer rate. It is argued that deficiency of micronutrients, such as dietary antioxidants or folate, is a major contributor to human cancer and degenerative diseases.Understanding the role of mitogenesis in mutagenesis is critical for clarifying the mechanisms of carcinogenesis and interpreting high-dose animal cancer tests. High-dose animal cancer tests have been done mainly on synthetic industrial chemicals, yet almost all of the chemicals humans are exposed to are natural. About half of natural chemicals tested in high-dose animal cancer tests are rodent carcinogens, a finding that is consistent with the view that high-dose tests frequently increase mitogenesis rates. Animals have numerous defenses against toxins that make them very well buffered against low doses of almost all toxins, whether synthetic or natural.