Chemical carcinogenesis and experimental models using human tissues

The majority of human cancer is caused by environmental agents including chemical carcinogens. These chemical carcinogens are both naturally-occurring compounds and products of an industrialized society. Most of the environmental chemical carcinogens require enzymatic activation into electrophilic metabolites which readily react with cellular macromolecules leading, in some cases, to malignant transformation of target epithelial cells. Model systems for studying carcinogenesis in human target tissues are being developed to link investigations using experimental animals with human cancer. Metabolism of chemical carcinogens is being studied in human tissues maintained in these model systems. For example, a marked variation among individuals in their capacity to metabolize carcinogenic polynuclear aromatic hydrocarbons has been observed. This inter-individual variation may, in part, be due to genetic factors. Model systems using human tissues should be useful in several areas of cancer research including: 1) identifying environmental carcinogens, their metabolic pathways and host factors determining susceptibility; and 2) testing new methods of prophylatic intervention in populations at high risk of developing cancer.