Phenol red inhibits growth of renal epithelial cells

Phenol red coeluted with a novel kidney cell growth factor during its isolation from conditioned medium by high-performance liquid chromatography. The possibility that phenol red rather than the putative factor mediated the growth-promoting activity was tested, because this pH indicator is known to possess estrogenic properties including a mitogenic effect. Unexpectedly, phenol red at the concentration found in Dulbecco's modified Eagle's medium (DMEM) inhibited growth of monkey (BSC-1) and canine kidney (MDCK) epithelial cells by 20-30%, but stimulated multiplication of 3T3 fibroblasts. The growth-inhibitory effect of phenol red for BSC-1 cells was reversible, concentration dependent, and cell-density independent when multiplication was examined in the presence and absence of the dye. Phenol red partially masked the mitogenic effect of calf serum and epidermal growth factor and was additive to the growth-inhibitory effect of transforming growth factor-beta 2. These observations indicate that phenol red at the concentration in DMEM both underestimates the potency of mitogens and overestimates the strength of an inhibitor of kidney epithelial cell growth and suggest that the dye be omitted from the culture medium when a new growth-regulatory compound is under study.