An in vivo/in vitro comparison of the pharmacodynamics of 3,3{prime},4,4{prime}-tetrachlorobiphenyl (PCB77)

The rat hepatoma H4IIE cells are used as a valuable tool to assess the toxicity of environmental samples containing chlorinated hydrocarbons. PCB exposure induces CYPIAI expression in both this cell line and the rat. The objective of this study was to investigate the quantitative dosimetry of PCB77 in the rat liver and the rat hepatoma cells, and to compare in vivo and in vitro P-450 IAI enzyme induction. Dose response studies on Day 3 in vitro and in vivo were carried out using UL-{sup 14}C-14-PCB77. H411E cells were exposed with various concentrations of PCB77 (0.0316--9.5 ng) and harvested on Day 3 and PCB77-derived radioactivity and ethoxyresorufin O-deethylase (EROD) activity were determined. Male Fisher rats were dosed by a single intraperitoneal injection with different concentrations of PCB77 (0.1--50 mg), and sacrificed on Day 3 and concentration of PCB77 in the rat liver and EROD activity were measured. The dose response study of EROD activity versus PCB77-derived radioactivity in the rat liver or in the hepatoma cells showed that there was a strong correlation on EROD induction between the H4IIE cells and the liver. This study demonstrates that rat hepatoma cells can mimic the behavior of enzyme induction in the liver ofmore » rats exposed to PCB77.« less