Is correction for protein concentration appropriate for protein adduct dosimetry? Hypothesis and clues from an aflatoxin B1-exposed population.
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.
Peng
Tao
T
Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China.
Li
Le-Qun
LQ
Peng
Min-Hao
MH
Liu
Zhi-Ming
ZM
Liu
Tang-Wei
TW
Yan
Lu-Nan
LN
Shen
Han-Ming
HM
Wang
LianWen
L
Wang
Qiao
Q
Wang
Kai-bo
KB
Liang
Ren-xiang
RX
Wei
Zong-liang
ZL
Ong
Choon Nam
CN
Santella
Regina M
RM
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
D000418:Albumins; D015415:Biomarkers; D016604:Aflatoxin B1