In Vivo/in VitroComparison of the Pharmacokinetics and Pharmacodynamics of 3,3′,4,4′-Tetrachlorobiphenyl (PCB77)
| Autor: | Donald E. Tillitt, Kyung O. Yu, Janusz Z. Byczkowski, Stephen R. Channel, Carlyle D. Flemming, Jeffrey W. Fisher, G. Allen Burton, Joanne M. Drerup |
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| Rok vydání: | 1996 |
| Předmět: |
Male
Pharmacology Dose-Response Relationship Drug Stereochemistry Cytochrome P450 Biology Toxicology Polychlorinated Biphenyls Rats Inbred F344 In vitro Rats Pharmacokinetics In vivo Cell culture Enzyme Induction Toxicity Cytochrome P-450 CYP1A1 Tumor Cells Cultured biology.protein Animals Toxicokinetics Enzyme inducer |
| Zdroj: | Toxicology and Applied Pharmacology. 141:434-438 |
| ISSN: | 0041-008X |
| Popis: | 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 compare in vitro and in vivo P4501A1 enzyme induction responses. For the 4-day time–course study, H4IIE cells were exposed with two doses of [ 14 C]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 ethoxyresorufin 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, with the remainder in the media and adhering to the culture plates. For the dose–response study in 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 induction in vivo were 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 ( r 2 = 0.985) between them. Prior to this study, no information on quantitative dosimetry and EROD activities of PCB77 has been reported to validate the in vitro assay with in vivo data. |
| Databáze: | OpenAIRE |
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