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致癌作用

Carcinogenesis.

作者信息

Calvin M

出版信息

Naturwissenschaften. 1975 Sep;62(9):405-13. doi: 10.1007/BF00612091.

Abstract

An examination has been made of the major chemicals which are known to be carcinogenic, either in animals or in humans. As a result, a generalized type of chemical property seems to be a prerequisite for the carcinogenic activity. In most cases, this is some kind of reactive electrophilic intermediate produced directly from the carcinogen or from one of its immediate metabolites. This electrophilic reagent is generally a positively charged ion of some kind. In the case of the hydrocarbons it seems to be an incipient carbonium ion; in the case of nitrogen compounds, it is a corresponding nitronium ion. There are a number of possible substrate materials (nucleophilic) in a cells, but the dominant one which has been suspected is the nucleic acid component, either the DNA or the RNA. The bases of these materials all have extra pi electrons susceptible to attach by the electrophiles of the carcinogen. Such a modification, particularly of the DNA, could lead to either major or minor changes in the genetic composition of the cell. Minor changes are usually rectifiable or are not visible, and this would include a large variety of point mutations.

摘要

人们已对已知在动物或人类中具有致癌性的主要化学物质进行了研究。结果表明,某种普遍类型的化学性质似乎是致癌活性的先决条件。在大多数情况下,这是某种直接由致癌物或其一种直接代谢产物产生的反应性亲电中间体。这种亲电试剂通常是某种带正电荷的离子。就烃类而言,它似乎是一种初生碳正离子;就氮化合物而言,它是相应的硝鎓离子。细胞中有许多可能的底物物质(亲核体),但被怀疑起主要作用的是核酸成分,即DNA或RNA。这些物质的碱基都有额外的π电子,容易被致癌物的亲电体所附着。这种修饰,尤其是对DNA的修饰,可能会导致细胞基因组成的重大或微小变化。微小变化通常是可纠正的或不可见的,这包括各种各样的点突变。

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