L1210(A) mouse lymphoma cells depleted of glutathione with L-buthionine-S-R-sulfoximine proliferate in tissue culture.
L1210(A) mouse lymphoma cells have been adapted to long-term tissue culture in the presence of L-buthionine-S-R-sulfoximine in concentrations of 1-10 mM. As a result of the inhibitory action of this compound on the synthesis of gamma-glutamylcysteine, the dipeptide precursor of glutathione, the cells are depleted of more than 90% of their normal cellular glutathione content. The residual 10% seems to resist depletion at high concentrations of buthionine sulfoximine. Glutathione depleted cells proliferate at a rate similar to that of non-depleted cells, and show full viability. Upon transfer of cells into inhibitor-free medium, they fully regain their original glutathione content. It is concluded that these cells contain at least two pools of glutathione: a large cytoplasmic pool and a smaller, possibly mitochondrial, pool. It is further concluded that the large pool of cytoplasmic glutathione is not obligatory for cell growth and mitosis.
D000818:Animals; D019328:Buthionine Sulfoximine; D002451:Cell Compartmentation; D002455:Cell Division / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D046508:Culture Techniques; D005978:Glutathione / Q000502:physiology*; D007939:Leukemia L1210 / Q000378:metabolism*; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D013997:Time Factors
D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione