Jong-Won Kang

Effects of genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, and GSTT1 on the urinary levels of 1-hydroxypyrene and 2-naphthol in aircraft maintenance workers

This study was undertaken to investigate the effects of genetic polymorphisms of the cytochrome P450 1A1 (CYP1A1) and 2E1 (CYP2E1), and glutathione S-transferases mu (GSTM1) and theta (GSTT1) on urinary 1-hydroxypyrene and 2-naphthol levels, and to estimate the level of exposure to polycyclic aromatic hydrocarbons (PAHs) in aircraft maintenance workers. In 218 Korean aircraft maintenance workers, the geometric means of urinary 1-hydroxypyrene and 2-naphthol were 0.32 and 3.25 micromol/mol creatinine, respectively. These urinary concentrations were approximately at the upper limit of the general population. Mean urinary 2-naphthol concentrations were significantly different between smokers and non-smokers. CYP1A1 and GSTM1 were statistically significant in analyses on both 1-hydroxypyrene and 2-naphthol levels among smokers. The results suggest that smoking has more profound effects on urinary PAH metabolites than does genetic polymorphisms in this population, and that CYP1A1 and GSTM1 activity might be related to the metabolism of 1-hydroxypyrene and 2-naphthol.

Effects of Genetic Polymorphisms in Metabolic Enzymes on the Relationships between 8-hydroxydeoxyguanosine Levels in Human Leukocytes and Urinary 1-hydroxypyrene and 2-naphthol Concentrations

Effects of Genetic Polymorphisms in Metabolic Enzymes on the Relationships between 8‐hydroxydeoxyguanosine Levels in Human Leukocytes and Urinary 1‐hydroxypyrene and 2‐naphthol Concentrations: Yong‐Dae Kim, et al. Department of Preventive Medicine, College of Medicine, Chungbuk National University, South Korea—This study was designed to investigate the relationship between environmental exposure to polycyclic aromatic hydrocarbons (PAHs) and oxidative stress, and to evaluate the effects of cigarette smoking and the genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 on the relationship. The subjects of this study were 105 healthy Korean males without occupational exposure to PAHs. The 8‐hydroxydeoxyguanosine (8‐OHdG) level in leukocytes, and urinary 1‐hydroxypyrene (1‐OHP) and 2‐naphthol concentrations, were measured by high‐performance liquid chromatography. Genetic polymorphisms of CYP1A1, CYP2E1, GSTM1, NAT2 and UGT1A6 were identified by PCR and PCR‐RFLP methods. The 8‐OHdG level showed a significant correlation with the 1‐OHP concentration in all subjects (p< .001) and in smokers (p< .01), and with the 2‐naphthol level in nonsmokers (p< .01). The 8‐OHdG level was significantly higher in smoking rapid acetylators than in smoking slow or intermediate acetylators, and in individuals with the UGT1A6 wild‐type than in those with the UGT1A6 mutant genotype. Significant positive correlations between 8‐OHdG and 1‐OHP concentrations were found in subjects with every genotype of the CYP1A1 and CYP2E1 genes, with the GSTM1 null‐type, with the NAT2 genotype of a rapid acetylator, and with the UGT1A6 wild‐type, respectively. The urinary 2‐naphthol level significantly correlated with the 8‐OHdG level only in subjects with the GSTM1 null‐type. In conclusion, there is a significant correlation between the 8‐OHdG level in leukocytes and the urinary 1‐OHP concentration in the population not occupationally exposed to PAHs. This relationship is affected by genetic polymorphisms in PAH metabolic enzymes.

Correlation of Urinary 1-Hydroxypyrene and 2-Naphthol with Total Suspended Particulates in Ambient Air in Municipal Middle-School Students in Korea

Abstract The authors investigated Korean municipal middle school students to ascertain whether urinary 1-hydroxypyrene (1-OHP) and 2-naphthol–markers for polycyclic aromatic hydrocarbon (PAH) exposure–reflect PAHs in ambient air. The authors used the β-ray absorption method, which is an index of ambient-air PAH exposure, to collect total suspended participate (TSP) data. The authors measured urinary 1-OHP and 2-naphthol concentrations in 137 nonsmoking students in 4 municipal middle schools within 1 km of ambient air monitoring stations. The median concentrations of urinary 1-OHP and 2-naphthol in the study were 0.09 nmole/mol creatinine and 2.19 μmol/mol creatinine, respectively, and the geometric means were 0.10 nmole/mol creatinine and 2.47 μmol/mol creatinine, respectively. Urinary 1-OHP concentration did not correlate significantly with any TSP index. There were significant correlations between urinary 2-naphthol level and the daily mean TSP level calculated for 2 days before survey, for 1 day before survey, and for the day of survey. These data suggest that urinary 2-naphthol may be a good marker for inhalation exposure to PAHs in ambient air.

Utility of fractional exhaled nitric oxide (FENO) measurements in diagnosing asthma

BACKGROUND To facilitate the use of fractional exhaled nitric oxide (F(E)NO) as a clinical test, F(E)NO measurements need more clarification. AIM We sought to evaluate the yield of F(E)NO measurement for the diagnosis of asthma and identify the determinants of F(E)NO in children. METHODS Two hundred forty five consecutive steroid-naïve patients aged 8-16 years with symptoms suggestive of asthma were included. Children were evaluated using F(E)NO measurements, questionnaires, skin prick tests, spirometries, and methacholine challenge tests. RESULTS Asthma was diagnosed in 167 children. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) of F(E)NO measurements for the diagnosis of asthma at the best cutoff value of 22 ppb were 56.9%, 87.2%, 90.5%, and 48.6%, respectively. At a cutoff value of 42 ppb, specificity and PPV were all 100% but at the cost of very low sensitivity (23.4%) and NPV (37.9%). Both atopy and asthma were identified as independent risk factors associated with high F(E)NO. The association of asthma with high F(E)NO was found only in atopic children because F(E)NO was low in non-atopic children regardless of asthma status. Although highest F(E)NO was observed in atopic asthmatic patients, 28% of these patients had F(E)NO values lower than 22 ppb. CONCLUSION Atopic asthmatic patients with low F(E)NO values and non-atopic asthmatic patients were responsible for false-negative cases that might contribute to low sensitivity of F(E)NO measurements in diagnosing asthma. High specificity of F(E)NO measurements may help identify patients with atopic asthma among subjects with respiratory symptoms.

Ethanol-induced oxidative DNA damage and CYP2E1 expression in liver tissue of Aldh2 knockout mice.

Ethanol‐Induced Oxidative DNA Damage and CYP2E1 Expression in Liver Tissue of Aldh2 Knockout Mice: Yong‐Dae Kim, et al. Department of Preventive Medicine and Medical Research Institute, College of Medicine, Chungbuk National University, Republic of Korea—Excessive alcohol consumption is associated with increased risks of many diseases including cancer. We evaluated oxidative DNA damage in Aldh2 +/+ and Aldh2 –/– mice after they had been subjected to acute ethanol exposure. Olive tail moment, which was measured using a comet assay, was not increased by ethanol treatment in both Aldh2 +/+ and Aldh2 –/– mice. However, after controlling for the effect of ethanol exposure, the Aldh2 genotype was a significant determinant for Olive tail moments. Although the ethanol treatment significantly increased the hepatic 8‐OHdG generation in only Aldh2 +/+ mice, the level of 8‐OHdG was the highest in Aldh2 –/– ethanol treated mice. The increase in the level of 8‐OHdG was associated with hepatic expression of cytochrome P450 2E1 (CYP2E1). The levels of Olive tail moment and the hepatic 8‐OHdG in the Aldh2 –/– control group were significantly higher than those of the Aldh2 +/+ control group. The level of CYP2E1 in liver tissue showed a similar pattern to those of the oxidative DNA damage markers. This study shows that acute ethanol consumption increases oxidative DNA damage and that expression of CYP2E1 protein may play a pivotal role in the induction of oxidative DNA damage. The finding that oxidative DNA damage was more intense in Aldh2 –/– mice than in Aldh2 +/+ mice suggests that ALDH2‐deficient individuals may be more susceptible than wild‐type ALDH2 individuals to ethanol‐mediated liver disease, including cancer.