Microsomal metabolism of chemical carcinogens in animals and man.
As the first step in the interaction between chemical carcinogen and cell, it has been recognized that most carcinogens, being chemically inert, must be metabolically converted into reactive, electrophilic 'ultimate carcinogens'. Ironically, the enzymes that activate carcinogens are the same microsomal, drug-metabolizing enzymes, mostly mixed-function oxidases, whose primary function is the detoxification and disposal of foreign chemicals. From the limited data available, it appears that, qualitatively, animals and man metabolize carcinogens via very similar pathways. However, in animals as well as in man there are marked species-related and individual differences in the basal levels of microsomal metabolism as well as in its inducibility. Therefore, the extrapolation to man of existing animal data on metabolic activation and carcinogenesis of chemicals is at present impossible. However, it might be possible to detect 'high-risk' individuals, i.e., individuals who might be especially endangered by exposure to environmental carcinogens due to their high rate of metabolism (for instance, some cigarette smokers), by determinations of human microsomal metabolism in vitro, using human leucocytes, or in vivo, employing safe drugs which are metabolized in a similar way to carcinogens, as indirect indices for individual variations in microsomal metabolism.
D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D006801:Humans; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000378:metabolism; D013045:Species Specificity
D002273:Carcinogens; D011083:Polycyclic Compounds