Annals of Occupational and Environmental Medicine

Original Article

Effect of Genetic Polymorphisms of CYP2E1 and ALDH2 on the Relationship between the Levels of Urinary 8-Hydroxydeoxyguanosine and t,t-Muconic Acid: Yong Dae Kim, Jong Won Kang, Sang Yong Eom, Yan Wei Zhang, Sung Hoon Kim, Eun Young Kim, Chul Ho Lee, Jai Dong Moon, Heon Kim; Korean Journal of Occupational and Environmental Medicine 2007;19(2):164-170. Published online June 30, 2007; DOI: https://doi.org/10.35371/kjoem.2007.19.2.164

Abstract PDF: OBJECTIVES
This study was performed to investigate the effect of genetic polymorphisms on the oxidative genetic damage caused by benzene exposure in workers.
METHODS
We measured urinary t,t-muconic acid levels as a biomarker for benzene exposure and measured the level of urinary 8-OHdG to assess oxidative DNA damage in benzene-exposed healthy male workers. Genetic polymorphisms of ALDH2 and CYP2E1 were determined by TaqMan assay. We estimated Pearson correlation coefficients between urinary t,t-muconic acid and 8-OHdG according to the genetic polymorphisms of CYP2E1 and ALDH2.
RESULTS
There was a significant relationship between urinary t,t-muconic acid and 8-OHdG concentrations in overall subjects (R=0.532, p<0.001). Smokers showed a higher correlation coefficient between the markers than nonsmokers did (R=0.520 vs. 0.010). Individuals with CYP2E1 c1/c1 genotype also showed a higher correlation coefficient between them than those with CYP2E1 c1/c2 or c2/c2 genotypes (R=0.670 vs. -0.145). In multiple linear regression analysis including smoking status, sorbic acid intake, age and genetic polymorphisms of CYP2E1 and ALDH2 as the independent variables, urinary t,t-muconic acid showed a significant association with urinary 8-OHdG.
CONCLUSIONS
There was a significant correlation between urinary 8-OHdG and urinary t,t-muconic acid in benzene-exposed workers. This relationship was affected by genetic polymorphisms of CYP2E1and ALDH2.

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Original Article

Effects of Genetic Factor, Life Styles, and Diet on Urinary Hippuric Acid Excretion in Toluene Exposed Workers: Hyeon Woo Yim, Chung Yill Park, Young Man Roh, Kang Sook Lee, Jung Min Lee, Won Chul Lee, Se Hoon Lee, Chee Kyung Chung; Korean Journal of Occupational and Environmental Medicine 2000;12(3):405-420. Published online September 30, 2000; DOI: https://doi.org/10.35371/kjoem.2000.12.3.405

OBJECTIVES
The purpose was to investigate the distributions and the effects of genetic polymorphism of aldehyde dehydrogenase 2(ALDH2), cytochrome P450 1A1(CYP1A1), and cytochrome P450 2E1(CYP2E1) on the toluene metabolism.
METHODS
The subjects consisted of 160 workers who were exposed to toluene in different industries such as paint manufacturing, painting on steel and wood products, printing, bonding, and coating. The exposed toluene level was monitored by passive air sampler, and the questionnaire variables were age, sex, smoking, drinking, previous nights drinking, use of personal protective equipment, work duration, and taking benzoic acid containing food. The urinary hippurric acid collected in the end of shift was corrected by urinary creatinine concentration. The genotypes of ALDH2, CYP1A1, and CYP2E1 were investigated using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) methods with DNA extracted from venous blood.
RESULTS
The geometric mean and the geometric standard deviation of urinary hippuric acid concentration were 0. 44 g/g creatinine and 2. 80. The urinary hippuric acid concentration was significantly related to personal exposed toluene level among personal exposed toluene level, use of personal protective equipment, and benzoic acid containing food diet. The slope differences of the regression for ALDH2, CYP1A1, and CYP2El genetic polymorphism, age, smoking, and work duration tended to be significant. In multiple regression analysis, the regression coefficient of toluene, ALDH2, CYP1A1, CYP2E1 genetic polymorphism were significant.
CONCLUSIONS
Prom the above results, urinary hippuric acid level after toluene exposure was significantly affected by the genetic polymorphism of ALDH2, CYP1A1, CYP2E1. It is needed further investigation of the urinary hippuric acid level considering the effect of genetic polymorphism.

Citations

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Applications of CYP-450 expression for biomonitoring in environmental health
Ho-Sun Lee, Mihi Yang
Environmental Health and Preventive Medicine.2008; 13(2): 84. CrossRef
Past and Future Applications of CYP450-Genetic Polymorphisms for Biomonitoring of Environmental Toxicants
Bitna Yi, Ji-Yeon Yang, Mihi Yang
Journal of Environmental Science and Health, Part C.2007; 25(4): 353. CrossRef

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Original Article

ALDH2 Genetic Polymorphism and Urinary Hippuric Acid Concentration in Toluene Exposed Workers: Oh Choon Kwon, Ree Joo, Jung Jeung Lee, Chang Yoon Kim, Jong Hak Chung, Seong Yong Kim; Korean Journal of Occupational and Environmental Medicine 1997;9(2):332-340. Published online June 30, 1997; DOI: https://doi.org/10.35371/kjoem.1997.9.2.332

Abstract PDF: In this study we evaluated the effects of the genetic polymorphism of aldehyde dehydrogenase2 (ALDH2) on toluene metabolism and determined biological exposure indices (BEIs) for toluene by the genotypes of ALDH2. The study subject were 77 men workers who are handling toluene in a video tape manufacturing factory and a textile company. Through the face-to-face interview, the information about smoking and drinking behavior wag obtained. For determination of ALDH2 poly morphism, 5 ml of venous blood sample was obtained from each subject after informed consent. DNA was extracted from the buffy coat and ALDH2 genotyping were performed using a polymerase chain reaction (PCR) method. The genotype of ALDH2 was classified into the homozygous genotype of normal ALDH2 (NN), and the heterozygous genotype of normal and inactive ALDH2 (ND), and homozygous genotype of an inactive ALDH2(DD). The concentration of hippuric acid (HA), the main metabolite of toluene, was determined in urine specimens collected at the end of shift, corrected with creatinine (HA/C), and compared with BEI for toluene, which is 2.5 g/g creatinine. The personal exposure level of toluene were monitored, using personal air sampler and analyzed by gas chromatography. The frequencies of the three genotypes in this study subjects were, NN : 45 (58.4%), ND : 26 (33.8%) and DD : 6 (7.8%), and frequencies of the genotypes in the middle or heavy toluene exposure workers were not significantly different from those in the mild toluene exposure workers. The frequencies of the DD type of ALDH2 was lower among alcohol drinkers than among non-drinkers. The urinary HA concentration of DD group was significantly lower than that of the NN or ND group, which suggests that the HA formation from toluene decreased in DD group. Regression lines were used to estimate the BEIs of the NN, ND, and DD groups. NN : y = 0.0085x + 0.23, r = 0.90 ND : y = 0.0074x + 0.21, r = 0.85 DD : y = 0.0041x + 0.82, r = 0.83 The three regression lines revealed that the estimated urinary HA concentration of NN, ND, and DD groups at 377 mg/m3 toluene(TLV-TWA) exposure were 3.43, 3.00, and 2.37 g/g creatinine, respectively. The HA concentration of the NN, and ND group were higher than that of the ACGIH BEI (2.5 g/g creatinine) ; however, the HA level of DD group was lower than the BEI. These results suggests that the ACGIH BEI is not adequate to estimate the toluene exposure of the NN, ND and DD groups at the same time. Based upon those results, a new BEI for ALDH2 deficient workers may be necessary.

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Original Article

Effect of Aldehyde dehydrogenase2 (ALDH2) Genotypes in Urinary Hippuric Acid Excretion as a Biological Exposure Index of Toluene: Seong Sil Chang, Chung Yill Park, Kang Sook Lee, Young Man Roh; Korean Journal of Occupational and Environmental Medicine 1996;8(3):454-465. Published online December 31, 1996; DOI: https://doi.org/10.35371/kjoem.1996.8.3.454

Abstract PDF

We investigated toluene exposure level, urinary hippuric acid concentrations, subjective symptoms and genotype of ALDH2 DNA in 134 exposed workers and 53 nonexposed workers for evaluating the effect of ALDH2 polymorphism on toluene metabolism and urinary hippuric acid concentration as biological exposure indices (BEI) of toluene. The results were as follows; 1. The percentage of inactive genotype of ALDH2 in exposed workers was lower than that of exposed (P=0.081). 2. The percentages of exposed workers with inactive genotype did not have any significant difference by the increase of toluene exposure level or work duration. 3. The frequency of drinking, monthly and maximum amount of alcohol intake in workers with normal genotype were significantly higher than those with inactive genotype. 4. The urinary hippuric acid concentration of nonexposed workers ,with inactive genotype was significantly lower than that with normal genotype. Under 100 ppm of toluene, similar but statistically insignificant trends were found, while above that concentration of toluene, reverse but statistically insignificant trends were found. 5. The number of acute and chronic subjective symptoms were increased positively with the concentration of toluene in workers with normal genotype, but ho such trends were found in workers with inactive genotype. 6. The result of simple linear regression between toluene and urinary hippuric acid concentrations showed a very significant positive linear relation-ship. The mean hippuric acid concentration of nonoccupational exposure was 0.289+/-0.227 (0.062-0.516) g/l. Toluene exposure level unable to discriminate with nonoccupational exposure estimated from regression equation, it range from 7.29 to 9.87 ppm. Considering above all things, it was useful to estimate the exposure level of toluene by means of analysing urinary hippuric acid concentration in both genotype workers, but the biological exposure indices (BEI) of both genotypes were different from each other. The BEI of the total exposed workers was 2.76 g/ I, which was lower than current criteria 3.0g/ I (2.5 g/g Cr), and it also suggest that the BEI for the exposed workers in our country be lowered to the appropriate level after further study.

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Effects of Factors Associated with Urine Hippuric Acid Correction Values in Urinary Creatinine by HPLC and Jaffe Method and Specific Gravity HPLC Jaffe Method
Key-Young Kim, Jong-Gyu Kim, Ki-Nam Yoon, Wha-Me Park, Hun-Hee Park
Journal of Korean Society of Occupational and Environmental Hygiene.2015; 25(4): 493. CrossRef

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