Dipple A, Bigger C A
NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, MD 21702-1201.
Mutat Res. 1991 Mar-Apr;259(3-4):263-76. doi: 10.1016/0165-1218(91)90122-3.
The polycyclic aromatic hydrocarbon carcinogens are formed in the inefficient combustion of organic matter and contaminate foods through direct deposition from the atmosphere or during cooking or smoking of foods. These potent carcinogens and mutagens require metabolism to dihydrodiol epoxide metabolites in order to express their biological activities. In vitro studies show that these reactive metabolites can react with the bases in DNA with different specificities depending upon the hydrocarbon from which they are derived. Thus, the more potent carcinogens react more extensively with adenine residues in DNA than do the less potent carcinogens, with the result that mutation at A . T base pairs is enhanced for the more potent carcinogens. In the past few years, considerable clarification of the mechanism of metabolic activation have been achieved and the focus for the immediate future is expected to be on how the reactive metabolites actually bring about biological responses.
多环芳烃致癌物是在有机物不完全燃烧过程中形成的,并通过大气直接沉降或在食品烹饪或熏制过程中污染食品。这些强效致癌物和诱变剂需要代谢生成二氢二醇环氧化物代谢物才能发挥其生物活性。体外研究表明,这些活性代谢物能以不同的特异性与DNA中的碱基发生反应,具体取决于它们所衍生的碳氢化合物。因此,强效致癌物比弱效致癌物更广泛地与DNA中的腺嘌呤残基发生反应,结果是强效致癌物使A.T碱基对处的突变增加。在过去几年中,人们对代谢活化机制有了相当清晰的认识,预计在不久的将来,重点将放在活性代谢物如何实际引发生物反应上。