Adduct levels from benzo[a]pyrenediol epoxide: Relative formation to histidine in serum albumin and to deoxyguanosine in DNA in vitro and in vivo in mice measured by LC/MS-MS methods

作者：Westberg Emelie A C; Singh Rajinder; Hedebrant Ulla; Koukouves Georgios; Souliotis Vassilis L; Farmer Peter B; Segerback Dan; Kyrtopoulos Soterios; Tornqvist Margareta A^*

来源：Toxicology Letters, 2015, 232(1): 28-36.

DOI：10.1016/j.toxlet.2014.09.019

• DNA adduct
• Serum albumin
• Histidine adduct
• Benzo[a]pyrene diolepoxide
• HPLC/MS-MS

Stable and specific biomacromolecular adducts can be used to measure in vivo doses of reactive compounds. An LC/MS-MS method to measure adducts from the benzo[a] pyrene (BP) metabolite (+/-)-anti-BP-7,8-diol-9,10-epoxide ((+/-)-anti-BPDE) to His(146) in serum albumin (SA), earlier evaluated on in vitro alkylated human SA, was tested for its applicability to mouse. It was shown that (+)-anti-BPDE form BPDE-His adducts to mouse SA. The method was applied to samples from BP-exposed mice (100 mg/kg of body weight for 1, 3, 7 and 28 days). BPDE-His in SA was close to the limit of quantification and showed the highest level (13 fmol/mg) 3 days after exposure. The level was 400 times lower (calculated per gram macromolecule) than earlier measured level of BPDE-adduct to deoxyguanosine (dG) in DNA in the livers. The relative rate of formation of adducts from BPDE with His in SA and with dG in DNA was investigated. Quantification by LC/MS-MS of the adducts in human blood alkylated in vitro with (+/-)-anti-BPDE showed a 1850 times higher level of BPDE-dG compared to BPDE-His. The specific and stable BPDEadducts to His in SA are potential biomarkers of in vivo dose of BPDE, though this requires a considerable improved analytical sensitivity of the LC/MS-MS method.

• 出版日期2015-1-5