Influence of genetic susceptibility on the urinary excretion of 8-hydroxydeoxyguanosine of firefighters
Yun-Chul Honga, Hye-Sook Parka, Eun-Hee Hab
a Department of
Preventive Medicine, Inha University College of Medicine, Inchon, Korea, b Department of
Preventive Medicine, Ewha Women's University College of Medicine,
Seoul, Korea
Correspondence to: Dr Yun-Chul Hong, Department of Preventive Medicine, Inha University College of Medicine, 253 Yonghyun-Dong, Nam-Gu, Inchon, 402-751, Korea email ychong{at}dragon.inha.ac.kr
Accepted 12 November
1999
OBJECTIVES
Oxidative
DNA damage has been implicated in carcinogenesis. The DNA damage can be
assessed from the urinary excretion of the DNA-repair product
8-hydroxydeoxyguanosine (8-OH-dG). The factors were investigated that
influenced the excretion of urinary 8-OH-dG in 78 firefighters.
METHODS
53 Out of 78 firefighters were exposed to fire within 5 days of the study and 25 were not. 8-OH-dG was measured by ELISA and the distribution of the
genotypes of CYP1A1, CYP2E1, GSTM1, and GSTT1 was measured by
polymerase chain reaction.
RESULTS
The homozygous
wild type frequencies of CYP1A1 MspI, CYP1A1
ile-val, CYP2E1, GSTM1, and GSTT1 were 31.5%, 56.2%, 60.3%, 50.7%, and 53.4%, respectively. The geometric mean of urinary 8-OH-dG was
14.1 ng/mg creatinine in more active firefighters and 12.3 ng/mg
creatinine in non-exposed and less active subjects. Significantly increased concentrations of urinary 8-OH-dG were found to be associated with cigarette smoking, and 14% of the variation of 8-OH-dG was explained by cigarettes smoked per day. The CYP1A1
MspI, CYP1A1 ile-val, GSTM1, and GSTT1
genetic polymorphisms were not found to be significantly associated
with the urinary excretion of 8-OH-dG. However, the subjects carrying
the CYP2E1 mutant type excreted higher concentrations of 8-OH-dG and
there was a marginally significant interaction of GSTT1 with
firefighting activity. Multiple regression analysis confirmed that
smoking was the strongest predictor of excretion of 8-OH-dG. Age, body
mass index, and firefighting activity were not significant predictive
factors for urinary 8-OH-dG.
CONCLUSION
Smoking
and CYP2E1 gene polymorphism may be important factors in carcinogenesis
and the GSTT1 positive genotype may be a genetic susceptibility factor
in firefighters who are exposed regularly to various chemical carcinogens.
Keywords: firefighters; 8-hydroxydeoxyguanosine; susceptibility
© 2000 by Occupational and Environmental Medicine
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