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COMPARING ENVIRONMENTALLY RELEVANT PCBS TO TCDD IN CYP1A2 NULL AND WILDTYPE MICE
Citation:
Burgin, D. E., J J. Diliberto, AND L S. Birnbaum. COMPARING ENVIRONMENTALLY RELEVANT PCBS TO TCDD IN CYP1A2 NULL AND WILDTYPE MICE. Presented at Society of Toxicology Annual Meeting, New Orleans, LA, March 06 - 10, 2005.
Description:
The role of CYP1A2 on the interactions of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin, dioxin), dioxin-like (DL) and non-dioxin-like (NDL) polychlorinated biphenyls (PCBs) was compared in multiple responses of different laboratory-defined mixtures, based on mass ratios found in food, using Cyp1a2 null (KO) and C57BL/6J wildtype (WT) male and female mice. The chemical groups were TCDD alone, DL Mix A, NDL Mix B, and combination Mix C and the doses ranged from 0.0, 0.001, 0.01, 0.1, 1.0, and 10.0 ug TEQ/kg body weight for Mix A, B and C, and the same plus 100.0 ug /kg for TCDD. Liver weight was increased only in Mix C in both male and female, WT and KO. No effects were observed in the KO mice on markers of oxidative stress. Both male WT and KO showed greater decreases in levels of total triiodothyronine (TT3), while Mix A and Mix C resulted in a 50% reduction in levels of total thyroxine (TT4) in all groups. With exposure to TCDD or DL mixes, but not to NDL PCBs, there was an increase in ascorbate levels. Based on these findings, there does not appear to be a strain difference in response to chemical exposure, indicating CYP1A2 is not required for these biochemical responses. However, there does appear to be a gender difference between the both the knockout and wildtype, reflecting a possible endogenous estrogenic component to maintenance of TT3 and ascorbic acid cycling levels. Based on these findings, it appears that CYP1A2 does play a role in the processes leading to increased liver weight, increased enzymatic induction, and disruption of thyroid homeostasis, but does not appear to play a role in responding to oxidative insult. Neither in the presence nor absence of CYP1A2 can the TEQ approach predict all effects measured when DL and NDL PCBs are present. (This abstract does not reflect EPA policy. DB supported by EPA CT902908 and NIEHS T32-ES07126)