Uptake of [U-14C]Lindane (γ-hexachlorocyclohexane) following exposure of isolated hepatocytes for short intervals of time

The initial steps of the uptake of lindane by the liver were studied by using isolated rat hepatocytes. U-¹⁴C]Lindane served as labeled indicator during the metabolite production. Results indicated a very fast uptake of the pesticide by the cells. During the first minute there were rapid exchanges between cells and medium; the rate of the uptake did not follow linear evolution. The metabolite production by the cells was time dependent. Up to eight metabolites were visualized during the first minute after the lindane addition. The time course of the uptake was concentration dependent. Profile evolution suggested that the cell metabolism was overloaded over 150 μM lindane. The depletion of hepatocytes in glutathion changed the partition of the radioactivity among the produced metabolites. At 37°C, the N₂ gassing decreased the quantities of cyclohexane rings in the cells. This effect was reversed by preliminary addition of SKF 525A to the incubation medium; SKF 525A had no effect under O₂ aeration. Isomers α and β of HCH, bromsulfophtalein interfered with the lindane transformation by the cells. Thus, isolated hepatocytes represented a sensitive intermediate preparation between perfused liver and homogenate experiments. They will be used for further comparison of the in vivo and in vitro metabolite formation corresponding to the elimination of lindane by the biliary pathway.