Cell cycle regulation by environmental pH

Purified populations of quiescent human tumour cells were isolated from plateau phase cultures of PMC-22 cells by centrifugal elutriation. Dilution into fresh medium resulted in these quiescent cells entering S phase exponentially with a t1/2 of 12 hr, after a 18-20-hr lag period during which cellular RNA content increased. Subsequent studies showed that recruitment of quiescent cells into the cell cycle could be regulated by extracellular pH. When exponentially growing PMC-22 cells were exposed to acidic extracellular pH levels, three growth patterns were observed: 1) Normal growth between pH 7.2 to pH 6.8; 2) A reduction in growth rate associated with accumulation of cells with a G1 DNA content between pH 6.7 and 6.4 (this was also shown to occur in a number of other tumour cell lines); 3) Non-cell-cycle-phase-specific arrest of growth at pH levels less than 6.3. Further studies with purified quiescent cell populations showed the possible existence of a pH-dependent restriction point in the G1 phase of these tumour cells. The implications of these observations to tumour biology are discussed.