Mechanism of action of food-associated polycyclic aromatic hydrocarbon carcinogens.
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.
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NCI-Frederick Cancer Research and Development Center, ABL-Basic Research Program, MD 21702-1201.
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D000818:Animals; D001483:Base Sequence; D002273:Carcinogens / Q000378:metabolism / Q000633:toxicity*; D003296:Cooking; D004247:DNA / Q000187:drug effects; D004852:Epoxy Compounds / Q000633:toxicity; D005506:Food Contamination; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009153:Mutagens / Q000378:metabolism / Q000633:toxicity*; D011083:Polycyclic Compounds / Q000633:toxicity*
D002273:Carcinogens; D004852:Epoxy Compounds; D009153:Mutagens; D011083:Polycyclic Compounds; D004247:DNA