Biology Faculty Articles


Specific genetic loci as targets of carcinogens and tumor promotors in mammals

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Journal of Environmental Pathology and Toxicology





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The basic advances in molecular biology and biochemical genetics in the last decade have shed new light on the physiological processes of cells during development, the organization of gene action, and the dysfunction of such cells which have become transformed. We present here a brief review of the various classes of cellular genes which are associated with neoplasia with emphasis on their candidacy as sub-chromosomal targets of carcinogens. The methodology of the detection and mode of action of these genes is discussed as they relate to the transformation event. Although few carcinogen tests at present are aimed at single genes, we feel that in the future they may and should be since a strictly defined carcinogen-testing protocol would ultimately be easier to interpret for purposes of assignment of human risk. The second part of this report is concerned with the question of inbred vs. outbred mice as a model system for human carcinogenesis. Since outbred mice more closely approximate the polymorphic gene pool of man, it has been suggested that outbred animals might be a better test population for carcinogens than inbred mice. The arguments states that inbred mice are more likely to be fixed for genes which aggravate or abrogate carcinogenic action leading to false results. We address here simply the question of how inbred the supply-house maintained populations of outbred mice become after decades of breeding in a controlled laboratory situation. We specifically present a preliminary estimate of the nature and extent of genic variability of Swiss-Webster mice as compared to wild mice and human populations.

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