Patterns of methionine auxotrophy in normal and neoplastic cells: the methionine independence of lymphocyte mitogenesis and low frequency of the methionine-dependent phenotype in human tumors.
Seven murine and 17 human tumor-derived cell lines were tested for their ability to grow in methionine-free medium containing the methionine precursor homocysteine. Three murine tumors, SP1, MDAY-D2, and L1210, failed to grow in this medium and were therefore methionine dependent (Met-Dep). In contrast, all human tumors, including 8 recently established cell lines, were methionine independent (Met-Indep). Concanavalin A-induced lymphocyte mitogenesis was also Met-Indep but required 3 to 4 times the amount of homocysteine needed for the growth of normal fibroblasts or Met-Indep tumors. In addition, lymphocyte mitogenesis was also supported by exogenous 5'-methylthioadenosine, another methionine precursor formed during polyamine synthesis. In contrast, Met-Dep tumors did not respond to increasing homocysteine concentration, nor was their growth supported by 5'-methylthioadenosine. These findings demonstrate that Met-Dep can occur by varied mechanisms relating to such parameters as homocysteine concentration and the ability of cells to generate Met-Indep revertants or to grow in 5'-methylthioadenosine. In general, we found the Met-Dep phenotype to be more common in murine tumor cells and to occur infrequently in human tumors. This may imply a species difference in methionine metabolism.
Judde
J G
JG
Department of Cell Biology, University of Texas, M.D. Anderson Cancer Center, Houston 77030.
Frost
P
P
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003470:Culture Media; D003839:Deoxyadenosines; D006801:Humans; D008213:Lymphocyte Activation; D008715:Methionine / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D009369:Neoplasms / Q000473:pathology*; D010641:Phenotype; D013872:Thionucleosides / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000473:pathology
D003470:Culture Media; D003839:Deoxyadenosines; D013872:Thionucleosides; C008500:5'-methylthioadenosine; D008715:Methionine; D000241:Adenosine