Interaction between quercetin, TPA and DDT in the V79 metabolic cooperation assay.

An in vitro assay measuring inhibition of metabolic cooperation between 6-thioguanine sensitive and 6-thioguanine resistant Chinese hamster (V79) cells in co-culture was used to detect chemically induced inhibition of gap-junctional intercellular communication. Inhibition of this cellular process by xenobiotics has been suggested to be an important event in tumour promotion. This study was undertaken to determine the effect on metabolic cooperation by the bioflavonoid quercetin alone and in co-exposure experiments with two recognized tumour promoters, the phorbol ester TPA and the organochlorine pesticide DDT. Furthermore, co-exposure experiments with TPA and DDT were performed. Quercetin alone did not affect metabolic cooperation at noncytotoxic doses. Treatment of the cells with either TPA, DDT or TPA together with DDT caused significant inhibition of metabolic cooperation. This effect was dose-dependently decreased by addition of quercetin. These findings suggest that quercetin inhibits or compensates a common effect induced by both TPA and DDT. Treatment of the cells with a fixed dose of TPA and increasing doses of DDT, or a fixed dose of DDT and increasing doses of TPA, caused significantly higher recovery of mutant cells than a calculated additive response. The data indicate that TPA and DDT induce a synergistic response with respect to affecting intercellular communication. The results suggest that there are different pathways of action for TPA and DDT.