title: Is correction for protein concentration appropriate for protein adduct dosimetry? Hypothesis and clues from an aflatoxin B1-exposed population.
abstract: Protein adducts are useful biomarkers for assessing exposure, metabolism and risk of carcinogens. Aflatoxin B1-albumin adducts (AAA) and protein carbonyl content (PCC) have long been used for assessing aflatoxin exposure and oxidative stress to proteins, and the quantitative data are almost exclusively expressed per mg protein. Given the large variation in protein concentrations in plasma among populations, this may not be the most appropriate method. The objective was to test the hypothesis that AAA and PCC should be expressed per mL plasma in population studies. AAA and PCC were analyzed among 402 subjects from three regions of China with a gradient in hepatocellular carcinoma (HCC) mortality ranging from 21 to 97 per 100,000. When biomarker values were expressed per mL plasma, the AAA level was significantly associated with plasma PCC (r = 0.262, P < 0.001), and adjusted levels of AAA and PCC paralleled HCC mortalities in the three regions, suggesting a role for aflatoxin-related oxidative stress in hepatocarcinogenesis in this population. In addition, there were statistically significant associations between both protein biomarkers, expressed per mL plasma, and the levels of alanine aminotransferase and aspartate aminotransferase in hepatitis B virus-infected subjects, suggesting roles for aflatoxin exposure, oxidative stress and hepatitis B virus infection in the development of HCC. The present data suggest that interindividual variation in plasma protein concentration may influence the dosimetry and relevant interpretation of protein biomarkers.
authors.affiliation: Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Peng
authors.forename: Le-Qun
authors.initials: LQ
authors.lastname: Li
authors.forename: Min-Hao
authors.initials: MH
authors.lastname: Peng
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Liu
authors.forename: Tang-Wei
authors.initials: TW
authors.lastname: Liu
authors.forename: Lu-Nan
authors.initials: LN
authors.lastname: Yan
authors.forename: Han-Ming
authors.initials: HM
authors.lastname: Shen
authors.forename: LianWen
authors.initials: L
authors.lastname: Wang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Wang
authors.forename: Kai-bo
authors.initials: KB
authors.lastname: Wang
authors.forename: Ren-xiang
authors.initials: RX
authors.lastname: Liang
authors.forename: Zong-liang
authors.initials: ZL
authors.lastname: Wei
authors.forename: Choon Nam
authors.initials: CN
authors.lastname: Ong
authors.forename: Regina M
authors.initials: RM
authors.lastname: Santella
mesh_terms: D000328:Adult; D016604:Aflatoxin B1 / Q000008:administration & dosage* / Q000494:pharmacology*; D000418:Albumins / Q000378:metabolism*; D015415:Biomarkers / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000139:chemically induced* / Q000378:metabolism* / Q000821:virology; D002681:China; D004781:Environmental Exposure; D005260:Female; D006801:Humans; D008297:Male; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects; D012307:Risk Factors
chemical_list: D000418:Albumins; D015415:Biomarkers; D016604:Aflatoxin B1