Growth kinetic studies of methionine dependence in co-culture of monolayer and anchorage independent mouse cell lines.
Non-transformed C3H/10T1/2 Cl 8 mouse embryo fibroblasts and malignant R.1.1 mouse T-lymphoma cells were examined for their ability to utilize homocysteine thiolactone (Hcy-tl) instead of methionine (Met) for growth. The non-transformed fibroblasts showed only a slightly slower growth rate in Hcy-tl supplemented medium, while the T-lymphoma cells showed an absolute requirement for Met, defined as methionine dependence. A co-culture system was established where both monolayer growing fibroblasts and lymphoma cells in suspension were grown in the same culture vessel. In Met supplemented medium both cell types proliferated, but when Hcy-tl replaced Met only the fibroblasts were able to grow. Two major conclusions were drawn: 1) The inability of the lymphoma cells to utilize Hcy-tl was not due to formation and release of toxic agent(s) to the growth medium. 2) It was possible to exploit the metabolic defect of methionine dependence to select for the growth of non-transformed cells from malignant cells.
Djurhuus
R
R
Department of Pharmacology and Toxicology, University of Bergen, Norway.
Ueland
P M
PM
D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D007700:Kinetics; D008223:Lymphoma; D008715:Methionine / Q000378:metabolism*; D051379:Mice; D008809:Mice, Inbred C3H; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000166:cytology* / Q000378:metabolism
D006710:Homocysteine; D008715:Methionine; C007957:homocysteine thiolactone