Chemical Carcinogen-Induced Changes in tRNA Metabolism in Human Cells
Interim technical rept. 1 Oct 1981-30 Sep 1982
OHIO STATE UNIV RESEARCH FOUNDATION COLUMBUS
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It was demonstrated that the nucleic acid catabolite 7-methylguanine a major product of many carcinogen methylation reactions as well as a natural component of RNA modulates tRNA modification by inducing queuine hypomodification. Phorbol ester tumor promoters were found to induce similar TRNA changes immediately preceding major phenotypic alterations in cultured human cells. Culture conditions were defined which allow normal human cells to mimic in vitro transformation in the continuous presence of active phorbol esters the characteristics of transformation induced include 5 to 10-fold increases in saturation density and anchorage-independent growth. Phorbol esters which are inactive as tumor promoters on mouse skin did not induce the phenotypic or biochemical changes in cultured human cells. Two-stage promotion was also demonstrated for certain agents e.g. norharman and anthralin subsequent to phorbol ester exposure. In addition, one or more new tRNA transglycosylases have been tentatively identified.
- Anatomy and Physiology
- Medicine and Medical Research