MITOGENIC AND INHIBITORY EFFECTS OF CARRIER AMPHOLYTES ON QUIESCENT AND STIMULATED HUMAN-DIPLOID LUNG FIBROBLASTS

Carrier ampholytes of various manufacture and pH ranges were found to have multiple effects on quiescent human diploid lung fibroblasts (MRC-5) when applied at a physiological pH. These effects varied, depending on dosage and pH range of the ampholytes, from the stimulation of the initiation of DNA synthesis in the absence of natural growth factors (LKB pH range 9-11, batches 11, 12, and 13, at 0.01-1.0 mg/ml) to inhibition of the mitogenic effect of platelet factor (all tested ampholytes >0.3 mg/ml). The higher dose levels of the alkaline-range ampholytes more particularly proved cytotoxic. These biological effects are lost more slowly than expected through dialysis tubing, so that separation of the ampholytes from the smaller natural mitogens, in the purification of which they may be used, needs careful monitoring. Characterization of the structure of the active ampholyte(s) may prove extremely useful in understanding the action of mitogens and in providing a synthetic stimulant to cell replication. Fractionation of the pH 9-11 range Ampholines suggests that the biological effects may be caused by many members of this complex mixture of substances, but the greatest activity was found in fractions with isoelectric points in the range 10.4-10.9. © 1979.