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Elevated overall rates of transmethylation in cell lines from diverse human tumors

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Editor's Statement This report describes increased rates of transmethylation in a large number of human tumor cell lines in culture, compared to transmethylation rates of several strains of untransformed human fibroblasts. All studies of this kind, using tumor cell lines of epithelial origin and employing as controls “normal” (untransformed) cell strains that are solely of fibroblastic origin, are difficult to interpret and remain open to question. However, the authors' observations that cell lines derived from both sarcomas and carcinomas exhibit enhanced transmethylation rates may strengthen, the case somewhat. More importantly, the potential relationship discussed by the authors of enhanced transmethylation rates to the phenomena of methionine dependence and unbalanced tRNA methylation make the data presented worthy of note. Gordon H. Sato

Summary

In a study of a diverse set of human tumor cell lines previously shown to all have a defect in methionine metabolism (Stern, P. H., Wallace, C. D. and Hoffman, R. M. J. Cellular Physiology119, 29–34, 1984), we demonstrate in this report that all have enhanced overall rates of transmethylation compared to normal human fibroblasts. Transmethylation rates were measured by blocking S-adenosylhomocysteine hydrolase and measuring the AdoHcy which accumulates as a result of transmethylation. The enhanced transmethylation rates may be the basis of the above-mentioned defects in methionine metabolism previously reported in human tumor cells, including the basis of the inability of the majority of the tumor cells to grow when methionine is replaced by homocysteine. The excess and unbalanced tRNA methylation observed for the last 25 years in many types of cancer may be at least in part explained by our results of elevated rates of overall transmethylation in cancer cells. The alteration of such a fundamental process as transmethylation in cancer may be indicative of its importance in the oncogenic process.

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Authors and Affiliations

  1. Department of Pediatrics, M-009, University of California, San Diego, 92093, La Jolla, California

    Peter H. Stern & Robert M. Hoffman

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  1. Peter H. Stern
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  2. Robert M. Hoffman
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Additional information

This study was supported by grants 1348A and 1496R1 from the Council for Tobacco Research-USA, Inc., grant CA27564 from the National Cancer Institute, and Research Career Development Award CA00804 from the National Cancer Institute, all to Robert M. Hoffman, and by the George A. Jacobs Memorial Fund for Cancer Research.

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Stern, P.H., Hoffman, R.M. Elevated overall rates of transmethylation in cell lines from diverse human tumors. In Vitro 20, 663–670 (1984). https://doi.org/10.1007/BF02619617

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