Cobalamin metabolism in methionine-dependent human tumour and leukemia cell lines.
OBJECTIVE
To identify the defect in cobalamin metabolism in the human melanoma cell line MeWoLC1, and to determine how frequent this defect is in other methionine-dependent tumour cell lines.


METHODS
Biochemical and somatic cell genetics study.


METHODS
Aspects of cobalamin metabolism were measured in a panel of 14 human tumour cell lines that were unable to proliferate normally in medium in which methionine had been replaced by its metabolic precursor homocysteine (methionine-dependent cell lines).


RESULTS
The human melanoma cell line MeWoLC1 was unique among these cell lines, in that it was characterized by decreased uptake of cobalamin, decreased synthesis of coenzyme derivatives, and decreased functional activity of the cobalamin-dependent enzymes methionine synthase and methylmalonylCoA mutase. This phenotype was identical to that observed in fibroblasts from patients with the cblC and cblD inborn errors of cobalamin metabolism. The defect in cobalamin metabolism in MeWoLC1 was complemented in somatic cell complementation analysis by cblA, cblB, cblD, cblE and cblG fibroblasts, but not by cblC fibroblasts, strongly suggesting that the defect in this cell line affects the cblC locus. Similar changes in cellular cobalamin metabolism were not seen in any other methionine-dependent cell line in the panel, suggesting that there may be multiple causes of methionine dependence, and that inactivation of the cblC locus may not be a common cause of this phenotype in transformed cells.


CONCLUSIONS
The defect underlying methionine dependence in MeWoLC1 appears to involve the locus that is affected in patients with the cblC inborn error of metabolism. This defect does not seem to be common among other methionine-dependent cell lines.
Watkins
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Department of Medicine, McGill University, Montreal, Que.
D002250:Carbon Radioisotopes; D003470:Culture Media; D006801:Humans; D007938:Leukemia / Q000378:metabolism*; D008545:Melanoma / Q000378:metabolism; D008715:Methionine / Q000096:biosynthesis* / Q000494:pharmacology; D009369:Neoplasms / Q000378:metabolism*; D011422:Propionates / Q000378:metabolism; D013763:Tetrahydrofolates / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014805:Vitamin B 12 / Q000378:metabolism*
D002250:Carbon Radioisotopes; D003470:Culture Media; D011422:Propionates; D013763:Tetrahydrofolates; D008715:Methionine; C029658:propionic acid; D014805:Vitamin B 12; C005984:5-methyltetrahydrofolate