3-Methylcholanthrene Induces Chylous Ascites in TCDD-Inducible Poly-ADP-Ribose Polymerase ( Tiparp ) Knockout Mice

• Published in: International journal of molecular sciences Vol. 20; no. 9; p. 2312
• Main Authors: Cho, Tiffany E, Bott, Debbie, Ahmed, Shaimaa, Hutin, David, Gomez, Alvin, Tamblyn, Laura, Zhou, Angela C, Watts, Tania H, Grant, Denis M, Matthews, Jason
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.05.2019; MDPI
• Subjects: 2,3,7,8-tetrachlorodibenzo-p-dioxin; 3-Methylcholanthrene; ADP-ribosylation; Ascites; chylous ascites; Corn oil; Cytochrome P450; Cytochromes P450; Deoxyribonucleic acid; DNA; DNA repair; Gene expression; Gene regulation; Immune system; Leukocytes (neutrophilic); Ligands; Liver; Localization; Metabolism; Metabolites; Neutrophils; Post-translation; Proteins; Regulatory sequences; Ribose; Ribosylation; Rodents; TCDD; TCDD-inducible poly-ADP-ribose polymerase (TIPARP); Toxicity; Viral infections; wasting syndrome; chylous ascites; wasting syndrome; 3-methylcholanthrene; 2,3,7,8-tetrachlorodibenzo-p-dioxin; TCDD-inducible poly-ADP-ribose polymerase (TIPARP)
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20092312

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. mice exhibit increased sensitivity to the toxicological effects of 2,3,7,8-tetrachlorodibenzo- -dioxin (TCDD), including lethal wasting syndrome. However, it is not known whether mice also exhibit increased sensitivity to other AHR ligands. In this study, we treated male 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 mice exhibited increased hepatic Cyp1a1 and Cyp1b1 levels compared with WT mice. No 3MC-treated 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 mice also exhibited a transient and mild hepatotoxicity with inflammation. 3MC-treated WT, but not mice, developed mild hepatic steatosis. Lipid deposits accumulated on the surface of the liver and other abdominal organs in the 3MC- mice. Our study reveals that mice have increased sensitivity to 3MC-induced liver toxicity, but unlike with TCDD, lethality is due to chylous ascites rather than wasting syndrome.