In Vivo Stimulation of Oxy Radicals by Mouse Skin Tumor Promoters
Our original suggestion in 1980 (1,2). that free radicals may be involved in tumor promotion was based on linkage of a number of puzzling observations about tumor promoters with newer insights into the biological and pathological role of free radicals. Of note was that the then known skin tumor promoters in the classic two-stage mouse skin tumor promotion system were all inflammatory agents. However, the lack of correlation among phorbol esters of tumor promoting ability with inflammation, as measured by standard techniques such as number of infiltrating inflammatoiy cells, seemed to preclude a role for inflammation in tumor promotion. Yet it was hard to ignore the many clinical observations, dating back to the nineteenth century, that inferentially seemed to point to chronic inflammation having some role in tumor development, observations ranging from the frequency of basal cell tumors on the bridge of the nose of eye glass wearers, to colorectal carcinoma in patients with ulcerative colitis. Our first approach to a possible role for free radicals in tumor promotion was to consider that the source of such free radicals in the mouse skin tumor initiation-promotion model might be derived from the activation of phagocytic cells, a known source of free radicals and active states of oxygen. Further, hepatic models of tumor promotion tend to feature compounds that are powerful inducers of cytochrome P-450 or of peroxisomes, both conceivably sources of free radicals or other active states of oxygen.
KeywordsPeritoneal Macrophage Phorbol Myristate Acetate Phorbol Ester Phagocytic Cell Tumor Promotion
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