Kinetics of G1 Progression in 3T6 and SV-3T3 Cells following Treatment by 25- Hydroxycholesterol1

The kinetics of cell cycle progression in continuously prolifer ating 3T3 fibroblasts and two tumor transformed derivatives (3T6 and SV 3T3 cells) following treatment by growth-factor deprivation (serum starvation) or 25-hydroxycholesterol were studied. Normal 3T3 cells were found to respond immediately (in the first cycle) to growth factor deprivation by leaving the cell cycle from Gì, whereas the tumor transformed derivatives did not. However, all three cell types were forced to stop the progression through the beginning of G, when treated by 25hydroxycholesterol. It was ensured that the doses of 25-hydrox ycholesterol used really induced substantial decrease of HMG CoA reducÃ-aseactivity. However, the effects of serum starvation on HMG CoA reducÃ-aseactivity varied considerably. In 3T3 cells HMG CoA reducÃ-aseactivity was substantially depressed, in 3T6 cells it was moderately depressed, and in SV-3T3 cells il was noi depressed al all. This difference of HMG CoA reducÃ-ase aclivity between 3T6 and SV-3T3 cells was related lo Ihe differ ence of growlh aclivily in serum-free medium. The data indicate that a certain activity of HMG CoA reducÃ-ase is required for the proliferalion of normal as well as lumor transformed cells but also lhal impairment of the conlrol of HMG CoA reducÃ-ase,leading lo increased enzyme aclivily, may resull in unconlrolled growlh in lumor Iransformed cells.