Since abnormal homocysteine metabolism is associated with several disorders of growth, including neoplasia, the metabolic fate of homocysteine thiolactone was studied in cell cultures from several malignant tumors, established cell lines, cell lines transformed by oncogenic viruses, and normal skin cells. In all of the cultures of malignant cells, homocysteine thiolactone became incorporated in peptide linkage with cellular proteins (thiolation). Normal cells incorporated the sulfur of homocysteine thiolactone only as the sulfate groups of proteoglycans. An established cell line incorporated homocysteine thiolactone in peptide linkage, but homocysteine thiolactone was released by acid hydrolysis. The findings suggest the speculative possibility that malignant cells are deficient in a homocysteine thiolactone derivative that prevents thiolation of proteins by homocysteine thiolactone. This hypothetical substance may also catalyze the synthesis of methionine and release acrolein, a growth-regulatory substance, in normal cells. The growth characteristics and tumorigenicity of cultured cells may be related to depletion of the hypothetical substance, and its identification, synthesis, and administration to animals would be expected to affect growth of malignant neoplasms.
Supported by Grants AM-15978 and CDA-HL-18747 from NIH and by Grant 73-655 from the American Heart Association.