Interspecies Sensitivity to Chemical Carcinogens: Relationships between MouseSkin Tumors and Human Lung Cancer

摘要

The review focuses on the relationships between mouse skin tumors and human lungcancer and discusses these relationships from several perspectives. These perspectives include: mouse skin as an experimental test system; metabolic comparisons of the response of mouse skin and human lung; comparison of DNA binding in mouse skin and human lung tissues; patterns of oncogene mutations in mouse skin and human lung cancers; quantitative comparison of the tumorigenic effects of complex mixtures; use of similarity to apply the comparative potency approach to new mixtures. In general, in terms of tumorigenic response, both mouse skin and human lung respond to a number of the same chemicals. Metabolically, it seems that both tissues are capable of metabolizing some of the major classes of chemicals carcinogens PAH's, nitrosamines to products that can bind to DNA. DNA adducts from exposures to complex mixtures are detected in both mouse skin and human lung tissues. A variety of mutations are found in the Ha-ras oncogene from the DNA from mouse skin tumors induced by chemical carcinogens and human lung tumor DNA seems to have similar mutations in the family of ras genes.