||Effects of Phorbol Myristate Acetate, Phorbol Dibutyrate, Ethanol, Dimethylsulfoxide, Phenol, and Seven Metabolities of Phenol on Metabolic Cooperation between Chinese Hamster V79 Lung Fibroblasts.
Malcolm, A. R. ;
Mills, L. J. ;
McKenna, E. J. ;
||Environmental Research Lab., Narragansett, RI. ;JRB Associates, Inc., Narragansett, RI. Marine Services Branch. ;Rhode Island Univ., Kingston. Dept. of Pharmacology and Toxicology.
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The discovery that phorbol ester tumor promoters inhibit metabolic cooperation (MC) between several cell types in vitro fostered the idea that the effect might be associated with tumor promoters in general. The authors are testing the hypothesis by assessing the effects of tumor promoters, selected metabolites, and other chemicals on MC between cocultivated mutant (HGPRT-) and wild-type (HGPRT+) V79 cells in reconstructed selection experiments. Correlation studies show that many structurally-diverse promoters inhibit MC in a dose-related fashion. More recent studies show that ethanol, a surface-active solvent with cocarcinogenic activity in humans, inhibits MC at high concentrations (10-20 mg/ml). Phenol, a weak promoter of tumors on mouse skin, has no effect on MC at concentrations ranging from 50 to 400 micrograms/ml. Five metabolites of phenol block MC, but at least two others appear to be inactive as complete promoters for mouse skin.