| First Author | Cho TE | Year | 2019 |
| Journal | Int J Mol Sci | Volume | 20 |
| Issue | 9 | PubMed ID | 31083300 |
| Mgi Jnum | J:284779 | Mgi Id | MGI:6391840 |
| Doi | 10.3390/ijms20092312 | Citation | Cho TE, et al. (2019) 3-Methylcholanthrene Induces Chylous Ascites in TCDD-Inducible Poly-ADP-Ribose Polymerase (Tiparp) Knockout Mice. Int J Mol Sci 20(9):2312 |
| abstractText | TCDD-inducible poly-ADP-ribose polymerase (TIPARP) is an aryl hydrocarbon receptor (AHR) target gene that functions as part of a negative feedback loop to repress AHR activity. Tiparp(-/-) mice exhibit increased sensitivity to the toxicological effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), including lethal wasting syndrome. However, it is not known whether Tiparp(-/-) mice also exhibit increased sensitivity to other AHR ligands. In this study, we treated male Tiparp(-/-) or wild type (WT) mice with a single injection of 100 mg/kg 3-methylcholanthrene (3MC). Consistent with TIPARP's role as a repressor of AHR signaling, 3MC-treated Tiparp(-/-) mice exhibited increased hepatic Cyp1a1 and Cyp1b1 levels compared with WT mice. No 3MC-treated Tiparp(-/-) mice survived beyond day 16 and the mice exhibited chylous ascites characterized by an accumulation of fluid in the peritoneal cavity. All WT mice survived the 30-day treatment and showed no signs of fluid accumulation. Treated Tiparp(-/-) mice also exhibited a transient and mild hepatotoxicity with inflammation. 3MC-treated WT, but not Tiparp(-/-) mice, developed mild hepatic steatosis. Lipid deposits accumulated on the surface of the liver and other abdominal organs in the 3MC-Tiparp(-/-) mice. Our study reveals that Tiparp(-/-) mice have increased sensitivity to 3MC-induced liver toxicity, but unlike with TCDD, lethality is due to chylous ascites rather than wasting syndrome. |
