Abstract
A relationship between formation of methylsulfonyl (MeSO2) metabolites of 2,2′,4,5,5′-pentachlorobiphenyl (PentaCB) and decrease in serum thyroxine (T4) level was examined in the rats and mice after a single i.p. injection of PentaCB (342 μmol/kg body weight). In either rats or mice, levels of the 3- and 4-MeSO2 metabolites of PentaCB in the liver and feces increased in a time-dependent fashion up to 8 days after PentaCB-treatment. However, there was a marked difference between rats and mice in the amount of the metabolites formed, and the cumulative amount of the either MeSO2 metabolite for 8 days after PentaCB treatment in the liver was 4 to 15 times higher in mice than in rats. On the other hand, a 40 to 60% decrease in level of serum total T4 occurred in both rats and mice at 1 day after PentaCB treatment, and the decrease was retained up to 8 days after PentaCB treatment. Thus, there was a marked difference between rats and mice in the formation of MeSO2 metabolites from PentaCB but not a significant difference between rats and mice in PentaCB-induced decrease in the level of serum total T4, indicating that PentaCB-induced decrease in the level of serum total T4 is not necessarily dependent on the MeSO2 metabolites formed.
Footnotes
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This work was supported in part by a Grant-in-Aid for Scientific Research (C) (no. 15510058, Y.K.; no. 16590101, K.H.; no. 17590104, M.D.) from Japan Society for the Promotion of Science, by a Health Sciences Research Grant for Research on Environmental Health (H11-Seikatsu-024, M.D.) from the Ministry of Health and Welfare of Japan, and by a Health and Labour Sciences Research Grants for Risk Analysis Research on Food and Pharmaceuticals (H13-Seikatsu-013, Y.K.) from Ministry of Health, Labour and Welfare of Japan.
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Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
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doi:10.1124/dmd.105.006189.
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ABBREVIATIONS: PCB, polychlorinated biphenyl; MeSO2, methylsulfonyl; PentaCB, 2,2′,4,5,5′-pentachlorobiphenyl; T4, thyroxine; TSH, thyroid-stimulating hormone; UDP-GT, UDP-glucuronosyltransferase; AUC, area under the curve.
- Received June 22, 2005.
- Accepted August 18, 2005.
- The American Society for Pharmacology and Experimental Therapeutics
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