Ko. Yu et al., IN-VIVO IN-VITRO COMPARISON OF THE PHARMACOKINETICS AND PHARMACODYNAMICS OF 3,3',4,4'-TETRACHLOROBIPHENYL (PCB77), Toxicology and applied pharmacology, 141(2), 1996, pp. 434-438
The rat hepatoma cell line, H4IIE, serves as a useful tool to assess p
otential biological effects such as induction of cytochrome P4501A1 ex
pression. The objectives of this study were twofold: to investigate th
e kinetic time course and dosimetry of PCB77 in rat hepatoma cells dos
ed with PCB77 and in liver of rats given ip doses of PCB77, and to com
pare in vitro and in vivo P4501A1 enzyme induction responses. For the
4-day time-course study, H4IIE cells were exposed with two doses of [C
-14]PCB77 (0.9 and 3 mu g/plate) and harvested at 15 and 30 min, 1, 2,
4, 8, and 12 hr, and 1, 2, 3, and 4 days. PCB77-derived radioactivity
was detected in the cells as early as 15 min postdosing. For the dose
-response study, the cells were dosed with various concentrations of P
CB77 (0.00316-5.37 mu g/plate) and harvested on Day 3 since ethoxyreso
rufin O-deethylase (EROD) activity in vitro reached its maximum on the
third day postdosing. Time-course and dose-response studies revealed
that only 1-3% of the total delivered dose was found in the cells, wit
h the remainder in the media and adhering to the culture plates. For t
he dose-response study in vivo, male Fischer rats were dosed with a si
ngle ip injection of various concentrations of PCB77 (0.1-50 mg/kg bod
y wt) and euthanized on Day 3. PCB77-derived radioactivity and EROD in
duction in vivo were measured. When EROD activity and PCB77-derived ra
dioactivity in the rat hepatoma cells and in the rat Liver were compar
ed on an equivalent weight basis, there was a significant correlation
(r(2) = 0.985) between them. Prior to this study, no information on qu
antitative dosimetry and EROD activities of PCB77 has been reported to
validate the in vitro assay with in vivo data. (C) 1996 Academic Pres
s, Inc.