The metabolic activation and nucleic acid adducts of naturally-occurring carcinogens: recent results with ethyl carbamate and the spice flavors safrole and estragole.
The metabolic activation and nucleic acid adducts of naturally-occurring carcinogens: recent results with ethyl carbamate and the spice flavors safrole and estragole.
复制标题
天然癌致癌物的代谢激活和核酸加合物：乙基氨基甲酸酯和香料味的最新结果。
DOI：
10.1038/bjc.1983.151
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发表时间：
1983-07
影响因子：
8.8
通讯作者：
Miller, E C
中科院分区：
文献类型：
--
作者：
Miller, J A;Miller, E C
一个小的（约30），但各种各样的有机和无机化合物似乎是人类和实验动物致癌。实验动物已知的化学致癌物的数量和种类要多得多，主要是合成有机化合物。这些物质包括绿色植物和真菌的一小部分（约30种）不同的代谢物。生物世界中一定存在着更多的致癌物质。与合成致癌物一样，这些天然存在的致癌物中的大多数是前致癌物，需要代谢转化为反应性亲电和致突变的最终致癌物。这些强亲电体联合收割机与靶组织中DNA、RNA、蛋白质和小分子中的亲核位点共价和非酶促结合。一种或多种DNA加合物似乎以不可逆的方式启动致癌作用。随后的促进步骤可通过进一步给予致癌物或通过用非致癌促进剂处理来完成，从而导致大体肿瘤。RNA和蛋白质加合物在致癌过程中的作用尚未被排除。最近关于天然致癌物氨基甲酸乙酯和某些烯基苯香料的体内代谢活化和反应性的数据说明了这些原理。在断奶前给予小剂量，这些药物可启动雄性小鼠肝脏的致癌过程。随后的肝脏生长和雄性激素因素似乎起着促进作用，导致一年后出现肉眼可见的肝脏肿瘤。反应性的亲电代谢产物的氨基甲酸乙酯和黄樟素和estragole和它们的核酸加合物在小鼠肝脏中形成的启动过程中已被表征。
A small (approximately 30) but varied group of organic and inorganic compounds appear to be carcinogenic in both humans and experimental animals. A much larger number and wider variety of chemical carcinogens, primarily synthetic organic compounds, are known for experimental animals. These agents include a small (approximately 30) and varied group of metabolites of green plants and fungi. Many more of these carcinogens must exist in the living world. As with the synthetic carcinogens, the majority of these naturally occurring carcinogens are procarcinogens that require metabolic conversion into reactive electrophilic and mutagenic ultimate carcinogens. These strong electrophiles combine covalently and non-enzymatically with nucleophilic sites in DNAs, RNAs, proteins, and small molecules in target tissues. One or more of the DNA adducts appear to initiate carcinogenesis in an irreversible manner. The subsequent promotion step leading to gross tumours may be completed by further administration of carcinogen or by treatment with non-carcinogenic promoters. Roles for the RNA and protein adducts in the carcinogenic process have not been excluded. Recent data on the metabolic activation and reactivity in vivo of the naturally occurring carcinogens ethyl carbamate and certain of the alkenylbenzene spice flavours are illustrative of these principles. These agents can initiate the carcinogenic process in male mouse liver with small doses given prior to weaning. Subsequent growth of the liver and male hormonal factors appear to function as promoters leading to gross hepatic tumors after one year. Reactive electrophilic metabolites of ethyl carbamate and of safrole and estragole and their nucleic acid adducts formed during initiation in mouse liver have been characterized.