Tumor promoters retard the loss of a transient subpopulation of cells in low passage Syrian hamster cell cultures

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Abstract
Early passage normal diploid Syrian hamster (SH) fetal cell cultures contain a transient subpopulation of contact‐insensitive (CS−) cells which lack density‐dependent inhibition of cell division. The size of this CS− subpopulation decreases during in vitro passage by conversion of the CS− cells to contact‐sensitive (CS+) cells. Approximately 10—15 population doublings after the frequency of the CS− cells has declined to below 0.001%, mass cultures cease proliferating and exhibit cellular senescence. Cultures with higher initial numbers of CS− cells exhibit longer in vitro proliferative life spans than cultures with smaller initial numbers of CS− cells. Active tumor promoting phorbol esters (12‐O‐tetra‐decanoyl‐phorbol‐13‐acetate [TPA] and phorbol‐12, 13‐didecanoate [PDD]) retard the decline in the proportion of CS− cells during in vitro passage, while the inactive tumor promoting phorbol ester, 4α‐phorbol‐12, 13‐didecanoate (4αPDD) has no effect on the rate of loss of the CS− cells. In addition, continuous treatment from secondary culture with TPA or PDD extends by approximately twofold the in vitro proliferative life span of SH fetal cell cultures. Treatment must, however, begin at passage 1 or 2 when the CS− cells are still present. After the proportion of the CS− cells has decreased to − cellular subpopulation, as well as an extention of in vitro proliferative life span, suggests that the conversion of CS− cells to CS+ cells is involved in the mechanism of in vitro senescence.
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