In vivo/in vitro comparison of pharmacokinetics and pharmacodynamics of 3,3',4,4'-tetrachlorobiphenyl (PCB77)

Toxicology and Applied Pharmacology
By: , and 

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Abstract

The rat hepatoma cell line, H4IIE, serves as a useful tool to assess potential biological effects such as induction of cytochrome P4501A1 expression. The objectives of this study were twofold: to investigate the kinetic time course and dosimetry of PCB77 in rat hepatoma cells dosed with PCB77 and in liver of rats given ip doses of PCB77, and to comparein vitroandin vivoP4501A1 enzyme induction responses. For the 4-day time–course study, H4IIE cells were exposed with two doses of [14C]PCB77 (0.9 and 3 μg/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 PCB77 (0.00316–5.37 μg/plate) and harvested on Day 3 since ethoxyresorufinO-deethylase (EROD) activityin vitroreached 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, with the remainder in the media and adhering to the culture plates. For the dose–response studyin vivo,male Fischer rats were dosed with a single ip injection of various concentrations of PCB77 (0.1–50 mg/kg body wt) and euthanized on Day 3. PCB77-derived radioactivity and EROD inductionin vivowere measured. When EROD activity and PCB77-derived radioactivity in the rat hepatoma cells and in the rat liver were compared on an equivalent weight basis, there was a significant correlation (r2= 0.985) between them. Prior to this study, no information on quantitative dosimetry and EROD activities of PCB77 has been reported to validate thein vitroassay within vivodata.

Additional publication details

Publication type Article
Publication Subtype Journal Article
Title In vivo/in vitro comparison of pharmacokinetics and pharmacodynamics of 3,3',4,4'-tetrachlorobiphenyl (PCB77)
Series title Toxicology and Applied Pharmacology
DOI 10.1006/taap.1996.0309
Volume 141
Issue 2
Year Published 1996
Language English
Publisher Elsevier
Contributing office(s) Columbia Environmental Research Center
Description 5 p.
First page 434
Last page 438