Oxidative DNA damage in peripheral leukocytes and its association with expression and polymorphisms of hOGG1: a study of adolescents in a high risk region for hepatocellular carcinoma in China.
OBJECTIVE
To study the oxidative DNA damage to adolescents of hepatocellular carcinoma (HCC) families in Guangxi Zhuang Autonomous Region, China.


METHODS
Peripheral leukocytes' DNA 7, 8-dihydro-8-oxoguanine (8-oxoG) and repair enzyme hOGG1 were quantified by flow-cytometry. hOGG1-Cys326Ser single nucleotide polymorphism (SNP) was distinguished by polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) assay.


RESULTS
There was a positive correlation between 8-oxoG and repair enzyme hOGG1 expression (P<0.001). HCC children (n=21) in Fusui county had a higher level of hOGG1 (P<0.01) and a lower level of 8-oxoG (P<0.05) than the controls (n=63) in Nanning city. Children in Nanning exposed to passive-smoking had a higher hOGG1 expression (P<0.05) than the non-exposers. 8-oxoG and hOGG1 were negatively correlated with body mass index, while hOGG1 was positively correlated with age. There was a peak of 8-oxoG level nearby the 12 year point. Individuals with the hOGG1 326Ser allele had a significantly marginal higher concentration of leukocyte 8-oxoG level than hOGG1 326Cys allele.


CONCLUSIONS
This is the first report using flow-cytometry to simultaneously quantify both the DNA oxidative damage and its repairing enzyme hOGG1. The results provide new insights towards a better understanding of the mechanisms of oxidative stress in a population highly susceptible to hepatocarcinogenesis.
Peng
Tao
T
Department of Hepatobiliary Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, China. pengpang@hotmail.com
Shen
Han-Ming
HM
Liu
Zhi-Ming
ZM
Yan
Lu-Nan
LN
Peng
Min-Hao
MH
Li
Le-Qun
LQ
Liang
Ren-Xiang
RX
Wei
Zong-Liang
ZL
Halliwell
Barry
B
Ong
Choon Nam
CN
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D015415:Biomarkers; D015992:Body Mass Index; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000378:metabolism*; D002681:China / Q000453:epidemiology; D004249:DNA Damage / Q000276:immunology*; D045647:DNA Glycosylases / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D005838:Genotype; D006147:Guanine / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism*; D008297:Male; D015999:Multivariate Analysis; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D015415:Biomarkers; C024829:8-hydroxyguanine; D006147:Guanine; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human