Carcinogenesis Advance Access originally published online on August 27, 2007
Carcinogenesis 2007 28(11):2347-2354; doi:10.1093/carcin/bgm193
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Evaluation of oxidative stress in a group of adolescents exposed to a high level of aflatoxin B1—a multi-center and multi-biomarker study



,*
1 Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Province, China
2 Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY 10032, USA
3 Department of General Surgery, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
4 Department of Community, Occupational and Family Medicine, National University of Singapore, Singapore 119260, Singapore
5 Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan
6 Fusui Cancer Institute, Fusui County 530021, Guangxi Province, China
* To whom correspondence should be addressed. Tel: 212 305 1996; Fax: 212 305 5328; Email: rps1{at}columbia.edu
The association between aflatoxin B1 (AFB1) exposure and oxidative stress was extensively examined in 84 adolescents from an area at high risk for hepatocellular carcinoma in China. Plasma level of aflatoxin B1–albumin adducts (AAAs) was associated with AFB1 excretion in urine (r = 0.394, P < 0.001). Urinary AFB1 was also associated with both the urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG) (r
0.479, P < 0.001) and 8-OHdG and hOGG1 levels in peripheral leukocytes (r
0.308, P
0.005). Similarly, AAA was significantly associated with both the urinary excretion of 8-OHdG (r
0.259, P
0.018) and the 8-OHdG and hOGG1 levels in peripheral leukocytes (r
0.313, P
0.004). In addition, urinary 8-OHdG was correlated with both the level of DNA 8-OHdG (r
0.24, P
0.05) and the expression of hOGG1 in peripheral leukocytes (r
0.429, P < 0.001). Protein carbonyl content (PCC) level was significantly associated with not only the level of DNA 8-OHdG (r
0.366, P < 0.001) and the urinary 8-OHdG (r
0.258, P
0.018) but also the expression of hOGG1 in peripheral leukocytes (r = 0.485, P < 0.001). A significant but weak association was found between high-performance liquid chromatograph–electrochemical detection (HPLC–ECD) and enzyme-linked immunosorbent assay (ELISA) for urinary 8-OHdG (r = 0.334, P = 0.002) and between HPLC–ECD and flow cytometry assays for 8-OHdG in leucocytes (r = 0.395, P < 0.001). Significant associations were observed between AAA and PCC and liver function indices (alanine aminotransferase and aspartate aminotransferase). These findings suggest significant contribution from AFB1 exposure to oxidative stress and subsequent repair among adolescents that may impose substantial risk for hepatocarcinogenesis in adulthood in this region.
Abbreviations: AAA, aflatoxin B1–albumin adduct; AFB1, aflatoxin B1; ALB, albumin; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BSA, body surface area; BW, body weight; ELISA, enzyme-linked immunosorbent assay; FCM, flow cytometry; HBV, hepatitis B virus; HCC, hepatocellular carcinoma; HPLC–ECD, high-performance liquid chromatograph–electrochemical detection; HV, hepatitis virus; 8-OHdG, 8-hydroxydeoxyguanosine; PCC, protein carbonyl content; ROS, reactive oxygen species; TP, total protein; WBC, white blood cell
These authors contributed equally to this work. Received April 25, 2007; revised July 24, 2007; accepted August 7, 2007.