The inhibition of tRNA methylase activity by nicotinamide and a non-dialyzable inhibitor.
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Biomedical subjects
Publications and source records attributed to R M Halpern.
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Walker-256 carcinosarcoma cells grown in tissue culture medium containing inhibitory DNA prepared from the tumor are shown to have an unaltered growth in vitro, but a diminished capacity to produce malignant tumors on injection into the rat. Coincident with this change in virulence is the induction of tRNA methylase inhibitors in these malignant cells. Within days after the DNA is removed from the growth medium, the tRNA methylase inhibitors disappear and the oncogenicity reappears.
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When malignant W-256 rat breast carcinosarcoma cells are mixed with an equal number of normal adult rat liver fibroblasts and allowed to grow in a medium containing sufficient L-methionine and an excess of vitamin B12 and of folic acid, the malignant cells outgrow the normal cells, and within 2 weeks the tissue culture flasks contain only neoplastic cells. However, when ample DL-homocystine or homocysteine replaces methionine in the medium containing the same amount of vitamin B12 and folic acid, and seeded with the same type and number of malignant and normal cells, the malignant cells die and the normal cells thrive. Substantiating this conclusion are the results of injections into rats of comparable numbers of cells from each group after 3 weeks of growth in tissue culture. Fatal malignancies are produced by the homocystein-cultivated cells.