title: Quantitative analysis of 3-OHB[a]P and (+)-anti-BPDE as biomarkers of B[a]P exposure in rats.
abstract: The aim of this study was to develop an analytical method for the determination the levels of metabolites of benzo[a]pyrene (B[a]P), 3-hydroxybenzo(a)pyrene (3-OHB[a]P) and (+)-anti-benzo(a)pyrene diol-epoxide [(+)-anti-BPDE, combined with DNA to form adducts], in rat blood and tissues exposed to B[a]P exposure by high-performance liquid chromatography with fluorescence detection (HPLC/FD), and to investigate the usefulness of 3-OHB[a]P and (+)-anti-BPDE as markers of intragastrical exposure to B[a]P in rats. The levels of 3-OH-B[a]P and B[a]P-tetrol I-1 released after acid hydrolysis of (+)-anti-BPDE in the samples were measured by HPLC/FD. The calibration curves were linear (r(2) > 0.9904), and the lower limit of quantification ranged from 0.34 to 0.45 ng/mL for 3-OHB[a]P and from 0.43 to 0.58 ng/mL for (+)-anti-BPDE. The intra- and inter-day stability assay data suggested that the method is accurate and precise. The recoveries of 3-OHB[a]P and (+)-anti-BPDE were in the ranges of 73.6 ± 5.0 to 116.5 ± 6.3% and 73.3 ± 8.5 to 141.2 ± 13.8%, respectively. A positive correlation was found between the concentration of intragastrical B[a]P and the concentrations of 3-OH-B[a]P and (+)-anti-BPDE in the blood and in most of the tissues studied, except for the brain and kidney, which showed no correlation between B[a]P and 3-OHB[a]P and between B[a]P and (+)-anti-BPDE, respectively. A sensitive, reliable and rapid HPLC/FD was developed and validated for analysis of 3-OHB[a]P and (+)-anti-BPDE in rat blood and tissues. There was a positive correlation between the concentration of 3-OHB[a]P or (+)-anti-BPDE in the blood and the concentration of 3-OHB[a]P or (+)-anti-BPDE in the most other tissues examined. The concentration of 3-OHB[a]P or (+)-anti-BPDE in the blood could be used as an indicator of the concentration of 3-OHB[a]P or (+)-anti-BPDE in the other tissues in response to B[a]P exposure. These results demonstrate that 3-OHB[a]P and (+)-anti-BPDE are potential biomarkers of B[a]P exposure, which would also be useful to assess the carcinogenic risks from B[a]P exposure.
authors.affiliation: College of Medical Laboratory, Dalian Medical University, Dalian, 116044, LiaoNing Province, China.|Harbin Infectious Disease Hospital, Harbin 150036, HeiLongJiang Province, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Lin
authors.affiliation: College of Medical Laboratory, Dalian Medical University, Dalian, 116044, LiaoNing Province, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Xiao-Chen
authors.affiliation: College of Medical Laboratory, Dalian Medical University, Dalian, 116044, LiaoNing Province, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Bo
authors.affiliation: College of Medical Laboratory, Dalian Medical University, Dalian, 116044, LiaoNing Province, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Na
authors.affiliation: College of Medical Laboratory, Dalian Medical University, Dalian, 116044, LiaoNing Province, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Min
authors.affiliation: College of Pharmacy, Washington State University, Spokane, WA, 99210-1495, USA.
authors.forename: Chen
authors.initials: C
authors.lastname: Gang
authors.affiliation: College of Medical Laboratory, Dalian Medical University, Dalian, 116044, LiaoNing Province, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Hui
authors.affiliation: Clincal Labortory, Dalian Municipal Friendship Hospital, Dalian, 116001, LiaoNing Province, China.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Jie
authors.affiliation: College of Medical Laboratory, Dalian Medical University, Dalian, 116044, LiaoNing Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Fa-Sheng
mesh_terms: D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D001580:Benzopyrenes / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D015415:Biomarkers / Q000032:analysis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D004781:Environmental Exposure / Q000032:analysis*; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D014018:Tissue Distribution
chemical_list: D001580:Benzopyrenes; D015415:Biomarkers; D001564:Benzo(a)pyrene; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; C021338:3-hydroxybenzo(a)pyrene
keywords: (+)-anti-benzo[a]pyrene-diol-epoxide; 3-hydroxy-benzo[a]pyrene; high performance liquid chromatography/Fluorescence Detection; rats