IN-VITRO INTERFERENCE WITH HEPATOCELLULAR TRANSPORT OF TAUROCHOLATE BY 1,1,2-TRICHLORO-1,2,2-TRIFLUOROETHANE

In recent years workers in our laboratory have shown that several indu strial chlorinated aliphatic hydrocarbon solvents interfere with the t ransport of bile acids by hepatocytes and this interference may accoun t for the raised concentration of serum bile acids that has been obser ved after occupational exposure to solvents. There has been concern ab out the effects on workers of a selective solvent used in degreasing e lectrical equipment, 1,1,2-trichloro-1,2,2-trifluoroethane (FC 113). H owever, this compound has not been investigated for effects on bile ac id transport. Therefore we undertook the present study to examine the direct in vitro effects of FC 113 on uptake and efflux of bile acids b y isolated rat hepatocytes. FC 113, at non-cytotoxic doses after a 20- min equilibration time, showed significant (P < 0.05) inhibitory effec ts on the initial rate of uptake of taurocholate (TC), whereas accumul ation of TC over an extended incubation time was not affected. Kinetic analysis revealed a non-competitive inhibition of TC uptake as eviden ced by a decline in V-max and an unaltered K-m. The initial rate of ef flux of TC and the continuous efflux of this model substrate from prel oaded cells incubated with different doses of solvent were not signifi cantly different from those of controls. However, the highest dose of solvent inhibited the process of efflux at the early time points. The data suggest that FC 113 interferes with bile acid transport in a reve rsible manner similar to that of the chlorinated aliphatic hydrocarbon s. It would be expected, therefore, that this solvent would cause an i ncrease in serum bile acids in exposed workers. Copyright (C) 1996 Els evier Science Ltd.