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INFLUENCE OF TYPE II DIABETES AND OBESITY ON THE DISPOSITION AND ELIMINATION OF TCDD IN MICE
DeVito, M J., J J. Diliberto, D. G. Ross, C. Emond, V. M. Richardson, AND L S. Birnbaum. INFLUENCE OF TYPE II DIABETES AND OBESITY ON THE DISPOSITION AND ELIMINATION OF TCDD IN MICE. Presented at Society of Toxicology 42nd Annual Meeting, Salt Lake City, Utah, March 9-13, 2003.
INFLUENCE OF TYPE II DIABETES AND OBESITY ON THE DISPOSTION AND ELIMINATION OF TCDD IN MICE. MJ DeVito', JJ Diliberto', DG Ross', C Emond2, VM Richardson', and LS Birnbaum', 'ETD, NHEERL, ORD, US EPA, RTP, NC, 27711, USA, 2National Research Council.
One possible explanation for the relationship between TCDD exposure and diabetes in some epidemiological studies may be that diabetics have slower elimination of TCDD compared to non-diabetics. The present study examines the effects of type II diabetes and body fat mass on the elimination of TCDD in mice. A high fat, high simple carbohydrate (HFHSC) diet was used to develop murine models of type II diabetes and obesity. After exposure to the HFHSC diet for 13 weeks, C57BL/6J mice develop obesity with signs of type II diabetes, while AJ mice develop greater body fat mass without alterations in serum glucose or insulin. Thus we can compare the effects of diabetes and body fat mass on the elimination of TCDD. After 13 weeks on either a normal or HFHSC diet male mice were exposed (po) to 5 ug 3H-TCDD/kg. Mice were killed 1, 3, 10, 20, 30, 40 and 60 days later and concentrations of TCDD were determined in blood, liver and fat. The elimination half-life of TCDD from the blood was similar in the C57 and AJ mice on the normal diet and the AJ mice on the HFHSC diet, 15.9, 17.9 and 14.9 days, respectively. C57 mice on the HFHSC diet had a blood half-life of 36.5 days. The HFHSC diet increased the liver half-life of TCDD from 9.8 to 23.8 days in the C57 mice, but did not significantly affect the hepatic elimination in the AJ mice. The half-life of TCDD from adipose tissue was slightly elevated by the HFHSC diet in C57 mice, 16.8 vs. 23.8 days, in the normal vs. the HFHSC diet. The HFHSC diet had no effect on the half-life of TCDD from adipose tissue in the AJ mice. These data suggest that type II diabetes may influence the half-life to TCDD and that this is independent of body fat composition. This work was funded in part by an Interagency Agreement with the USAir Force # FQ7624-00-YA085) and a cooperative agreement (CR 828790) with NRC. (This abstract does not represent USEPA policy).