title: Dimethylarsinic acid modulates the aryl hydrocarbon receptor-regulated genes in C57BL/6 mice: in vivo study.
abstract: 1. Dimethylarsinic acid (DMA(V)) is the major metabolite of inorganic arsenic in human body. Thus we investigated the effect of DMA(V) on the alteration of phase I (typified by Cyp1a) and phase II (typified by Nqo1) AhR-regulated genes in vivo. C57BL/6 mice received DMA(V) (13.3 mg/kg, i.p.) with or without TCDD (15 μg/kg, i.p.), thereafter the liver, lung, and kidney were harvested at 6 and 24 h post-treatment. 2. Results demonstrated that DMA(V) has no significant effect on Cyp1a mRNA and protein expression or catalytic activity in the liver. On the other hand, DMA(V) significantly potentiated the TCDD-mediated induction of Cyp1a mRNA and protein expression, with a subsequent potentiation of catalytic activity in the lung. Moreover, DMA(V) significantly inhibited the TCDD-mediated induction of Cyp1a mRNA and protein expression with subsequent inhibition of catalytic activity in the kidney. 3. Regarding to phase II AhR-regulated genes, DMA(V) has no significant effect on Nqo1 mRNA and protein expression, or activity neither in the liver, lung, or kidney. 4. In conclusion, the present work demonstrates for the first time that DMA(V) modulates AhR-regulated genes in a tissue- and enzyme-specific manner. This modulation may play a crucial role in arsenic-induced toxicity and carcinogenicity.
authors.affiliation: a Faculty of Pharmacy and Pharmaceutical Sciences , University of Alberta , Edmonton , AB , Canada.
authors.forename: Osama H
authors.initials: OH
authors.lastname: Elshenawy
authors.affiliation: a Faculty of Pharmacy and Pharmaceutical Sciences , University of Alberta , Edmonton , AB , Canada.|b Department of Pharmacology and Toxicology , Faculty of Pharmacy, Helwan University , Greater Cairo , Egypt , and.
authors.forename: Ghada
authors.initials: G
authors.lastname: Abdelhamid
authors.affiliation: a Faculty of Pharmacy and Pharmaceutical Sciences , University of Alberta , Edmonton , AB , Canada.|c Department of Pharmacology , College of Pharmacy, Prince Sattam Bin Abdulaziz University , Al Kharj , Kingdom of Saudi Arabia.
authors.forename: Hassan N
authors.initials: HN
authors.lastname: Althurwi
authors.affiliation: a Faculty of Pharmacy and Pharmaceutical Sciences , University of Alberta , Edmonton , AB , Canada.
authors.forename: Ayman O S
authors.initials: AOS
authors.lastname: El-Kadi
mesh_terms: D000818:Animals; D002101:Cacodylic Acid / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006540:Herbicides / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism*
chemical_list: D006540:Herbicides; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D002101:Cacodylic Acid; D016660:NAD(P)H Dehydrogenase (Quinone)
keywords: AhR; Cyp1a; DMA(V); Nqo1; arsenic; cacodylic acid; carcinogen-activating enzymes; dimethylarsinic acid