Agarose-selected variants of two human tumor cell lines exhibit altered methionine auxotrophy.
Our aim was to determine if the selection of human tumor cells with enhanced anchorage-independent growth capacity was associated with alterations in methionine auxotrophy. Cells with an increased ability to form colonies on soft agarose were selected from human melanoma (MeWo) and neuroepithelioma (SK-N-MC) cell lines. In contrast to their respective parental lines, a high proportion of the agarose-selected variants were completely unable to proliferate in methionine-free medium containing its immediate precursor homocysteine. The variants exhibited no significant change in their total DNA 5-methylcytosine content and showed no stimulation of either RNA or DNA synthesis upon the addition of homocysteine when the cells were cultured in methionine-free medium. These variants were unable to synthesize [3H]S-adenosylmethionine from [3H]adenine and homocysteine. The failure to detect the accumulation of [3H]S-adenosylmethionine in these variant lines was not likely due to the enhanced turnover of S-adenosylmethionine but rather to a reduced ability to synthesize methionine from homocysteine and 5-methyltetrahydrofolic acid. These results support our hypothesis that alterations in the metabolism of methionine and/or intracellular transmethylating activities may contribute to, or be associated with, the autonomous growth of malignant human tumor cells.
Liteplo
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RG
Department of Experimental Oncology, Ottawa Regional Cancer Centre, Ontario, Canada.
Hipwell
S E
SE
D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D014644:Genetic Variation; D006710:Homocysteine / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008715:Methionine / Q000378:metabolism*; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D009696:Nucleic Acids / Q000096:biosynthesis; D012436:S-Adenosylmethionine / Q000378:metabolism; D012685:Sepharose; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D009696:Nucleic Acids; D006710:Homocysteine; D012436:S-Adenosylmethionine; D012685:Sepharose; D008715:Methionine