DNA adducts induced by food mutagen PhIP in a mouse model expressing human sulfotransferases 1A1 and 1A2. (25th April 2016)

• Record Type: Journal Article
• Authors: Høie, Anja Hortemo; Monien, Bernhard Hans; Glatt, Hansruedi; Hjertholm, Hege; Husøy, Trine
• Is Part Of: Toxicology letters. Volume 248(2016)
• Page Start: 34
• Page End: 38
• Publication Date: 2016-04-25
• Subjects: CYP cytochrome P450 -- 2′-deoxyguanosine-PhIP C8-(2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine-N2-yl)-2′-deoxyguanosine -- h human -- hSULT mice FVB mice expressing human sulfotransferases 1A1 and 1A2 -- NAT N-acetyltransferase -- PhIP 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine -- SULT sulfotransferase -- UPLC–MS/MS ultra performance liquid chromatography coupled with tandem mass spectrometry; Food processing contaminant -- Genotoxicity -- Sulfotransferase -- DNA adduct -- Liquid chromatography -- Mass spectrometry; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2016.02.017
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: C8-PhIP-dG adducts were quantified in hSULT mice by the sensitive method UPLC–MS/MS. hSULT mice had a 3-14-fold increase in adducts of liver, kidney and intestine. UPLC–MS/MS proves to be a reproducible and sensitive detection method for adducts. Abstract: Food processing contaminant 2-amino-1-methyl-6-phenylimidazo[4, 5- b ]pyridine (PhIP) has previously been shown to induce formation of DNA adducts in vivo . In a previous study the adduct levels were found to increase in a mouse model expressing human (h) sulfotransferases (SULTs) 1A1 and 1A2 after PhIP exposure, detected by 32 P-postlabelling. Isotope dilution ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC–MS/MS) is emerging as the method of choice for selective and reproducible detection of known DNA adducts. In the present study we investigated the level and distribution of PhIP induced DNA adducts in male FVB mice 9–11 weeks of age with hSULT mice or wild-type mice (wt) using UPLC–MS/MS. Mice received a single administration of 75 mg/kg bw PhIP by oral gavage, and DNA was analysed 3 h after exposure. C 8-(2-amino-1-methyl-6-phenylimidazo[4, 5- b ]pyridine- N 2 -yl)-2′-deoxyguanosine (C8-PhIP-dG) adduct levels are significantly higher in PhIP exposed hSULT mice compared with PhIP exposed wt mice. The liver was the least affected organ in wild-type mice, whereas it was the most affected organ in hSULT mice with a 14-fold higher adduct level.