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DISPOSITION OF TCDD IN A MOUSE MODEL OF OBESITY AND TYPE II DIABETESE
Citation:
Diliberto, J J., M J. DeVito, D. G. Ross, V. M. Richardson, AND L S. Birnbaum. DISPOSITION OF TCDD IN A MOUSE MODEL OF OBESITY AND TYPE II DIABETESE. Presented at Society of Toxicology Annual Meeting, New Orleans, LA, March 06 - 10, 2005.
Description:
Recent epidemiology studies have shown an association between type II diabetes and exposure to TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin). A possible explanation is that diabetics have a slower elimination of TCDD than non-diabetics. The objective of the present study was to examine the influence of diabetes and body fat mass on the disposition of TCDD using a mouse model of obesity and Type II diabetes. Male C57BL/6J (C57) and AJ/6 (AJ) mice were placed on a normal diet or a high fat, high simple carbohydrate (HFHSC) diet for 13 wks before the start of the study. The HFHSC diet was used to induce obesity and signs of type II diabetes in C57 mice; while AJ mice on a HFHSC diet became fatter than AJ/6 on a normal diet, but not obese nor hyperglycemic. Mice were then housed in metabolism cages and maintained on their respective diets throughout the study and given a single (po) dose of 5 ug [3H]TCDD/kg. After 40 days, mice (singly housed in metabolism cages with separate collection of urine and feces every 24h) were killed and tissues collected. Disposition in excreta and tissues was quantified. Percentages (?SD) of cumulative administered dose excreted were: in feces 50?5.4, 32?3.6, 48?2.3, 33?3.8; and in urine 22?2.0, 27?5.7, 15?1.5, 21?5.0 for C57 normal diet, C57 fat diet, AJ normal diet, and AJ fat diet, respectively. Percentages (?SD) of administered dose at 40 days post-dosing were: in liver 2.9?0.3, 6.7?1.2, 5.0?0.5, 5.5?1.3; and in adipose tissue 4.7?0.6, 28.3?4.1, 7.6?0.8, 21.7?3.2 for C57 normal diet, C57 fat diet, AJ normal diet, and AJ fat diet, respectively. Data from this study made clear the effects of body fat and diabetes on the deposition of TCDD in excreta and tissues, and showed that a high body fat mass slowed the elimination of TCDD. (This work was funded in part by an Interagency Agreement with the US Air Force #FQ7624-00YA085. This abstract does not represent USEPA policy.)