Interindividual Variation in Human Chemical Carcinogenesis: Implications for Risk Assessment

  • Curtis C. Harris


Chemical carcinogenesis is considered to be a multistage process involving genetic and epigenetic lesions that activate protooncogenes and inactivate tumor suppressor genes. Chemical carcinogens are generally activated enzymatically to electrophiles that form covalently bound carcinogen-DNA adducts. Detoxifying enzymes are competing with the activating enzymes for these procarcinogenic chemical substrates. Wide person to person variations in these two types of enzymatic activities are found. Repair rates of DNA damage caused by carcinogens also vary among individuals. These interindividual differences in the metabolism of chemical carcinogens and repair rates of carcinogen-induced DNA damage reflect acquired and inherited host factors that may influence an individual’s risk for development of cancer. Interindividual and intertissue variation in response to tumor promoters is currently unknown in humans but studies in animal models would suggest substantial variability may occur. The wide interindividual variations in the determinants of genetic damage involved in tumor initiation and conversion and the assumed diversity in response to tumor promoters should be incorporated into efforts in quantitative assessment of cancer risk.


Polycyclic Aromatic Hydrocarbon Lung Cancer Risk Interindividual Variation Chemical Carcinogen Xeroderma Pigmentosum 
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© Birkhäuser Boston 1990

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  • Curtis C. Harris

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