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Mercury and halogenated aromatic hydrocarbons (HAHs), typified by 2,3,7,8\u2010tetrachlorodibenzo\u2010p\u2010dioxin (TCDD), are persistent environmental pollutants involved in the modulation of aryl hydrocarbon receptor (AHR) gene battery, including cytochrome P450 (<jats:italic>CYP<\/jats:italic>) genes. We previously investigated the effect of coexposure to either inorganic or organic mercury (Hg<jats:sup>+2<\/jats:sup> and MeHg) with TCDD on CYP1A1 in vitro. Thus, we examined the impact of coexposure to Hg<jats:sup>+2<\/jats:sup> or MeHg and TCDD on AHR\u2010regulated genes (<jats:italic>Cyp1a1\/1a2<\/jats:italic>) in vivo and in vitro. Therefore, male C57BL\/6 mice were injected intraperitoneally with MeHg or Hg<jats:sup>+2<\/jats:sup> (2.5\u2009mg\/kg) in the absence and presence of TCDD (15\u2009\u03bcg\/kg) for 6 or 24\u2009h. The concentration\u2010dependent effect of MeHg was examined in murine hepatoma Hepa1c1c7 cells. In vivo, both MeHg and Hg<jats:sup>2+<\/jats:sup> inhibited the TCDD\u2010mediated induction of <jats:italic>Cyp1a1\/1a2<\/jats:italic> mRNA levels. However, Only Hg<jats:sup>2+<\/jats:sup> was able to inhibit the TCDD\u2010mediated induction at posttranscriptional levels of CYP1A1\/1A2 protein and catalytic activity, suggesting differential modulation effects by Hg<jats:sup>+2<\/jats:sup> and MeHg. In addition, the inhibitory role of HO\u20101 (Heme oxygenase\u20101) on CYP1A activity induced by TCDD was investigated using a HO\u20101 competitive inhibitor, tin\u2010mesoporphyrin, that partially restored the MeHg\u2010mediated decrease in CYP1A1 activity. This study demonstrates that MeHg, alongside Hg<jats:sup>2+<\/jats:sup>, can differentially modulate the TCDD\u2010induced AHR\u2010regulated genes (<jats:italic>Cyp1a1\/1a2<\/jats:italic>) at different expression levels in C57BL\/6 mice liver and Hepa1c1c7 cells.<\/jats:p>","DOI":"10.1002\/jbt.23243","type":"journal-article","created":{"date-parts":[[2022,10,17]],"date-time":"2022-10-17T07:54:39Z","timestamp":1665993279000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mercury and methylmercury differentially modulate hepatic cytochrome P450 1A1 and 1A2 in vivo and in vitro"],"prefix":"10.1002","volume":"37","author":[{"given":"Mohammed A.","family":"Alqahtani","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, 2142\u2009J Katz Group\u2010Rexall Centre for Pharmacy and Health Research Edmonton University of Alberta Ringgold Standard Institution Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud A.","family":"El\u2010Ghiaty","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy and Pharmaceutical Sciences University of Alberta Edmonton Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8692-0400","authenticated-orcid":false,"given":"Ayman O. 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