The reversible inhibition of myoblast proliferation by gamma-hexachlorocyclohexane

The effects of treating non-fusing myoblast variants, fu-1 and M3A, with two levels (1 X 10(-4) M and 2 X 10(-4) M) of gamma-hexachlorocyclohexane, an inhibitor of phosphatidylinositol synthesis, on myoblast proliferation were evaluated by measuring myoblast proliferation (counting cells) and visual inspection via phase microscopy. In the presence of gamma-hexachlorocyclohexane, these cells were arrested, presumably in G1. The inability of these cells to replicate did not appear to be due to a toxic effect of gamma-hexachlorocyclohexane, because these cells were capable of resuming proliferation once they were transferred to media lacking gamma-hexachlorocyclohexane. Cells were grown in media containing myo-[2-3H]inositol and the radioactive content of water-soluble metabolites, the end product of phosphatidylinositides hydrolysis, was quantitated. Cells were grown in the presence of gamma-hexachlorocyclohexane, in addition to the loss of proliferative ability, also contained significantly less water-soluble metabolites. Therefore, it appears that there is a direct relationship between phosphatidylinositol metabolism and cell proliferation in the cell lines studied.