크실렌 노출로 인한 요중 메틸마뇨산 배설에 미치는 유전자 다형성 연구

김청식,고상백,김형수,박수경,장성훈,Kim, Cheong-Sik,Koh, Sang-Baek,Kim, Hyeong-Su,Park, Sue-Kyung,Chang, Soung-Hoon 대한예방의학회 2004 예방의학회지 Vol.37 No.4

Objectives : The purpose of this study was to investigate the effect of genetic polymorphism of cytochrome P450 2E1 (CYP2E1) and aldehyde dehydrogenase 2 (ALDH2) on the xylene metabolism. Methods : Among 247 workers, 116 were occupationally exposed to xylene and 131 were not. Workers exposed to xylene had different work such as spray, touch-up, mix & assist, and pre-treat. Questionnaire variables were age, sex, use of personal protective equipment, smoking, previous night's drinking and work duration. The urinary methylhippuric acid was measured in the urine collected in the afternoon and corrected by urinary creatinine concentration. The genotypes of CYP2E1 and ALDH2 were investigated by using PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) methods with DNA extracted from venous blood. Results : 1. The urinary concentrations of o-, m-, and p-methylhippuric acid and total methylhippuric acid in the exposed group were significantly higher than those in the non-exposed group (p<0.001). 2. In multiple regression analysis, the urinary methylhippuric acid concentration was significantly influenced by exposure grade (Job-exposure matrixes), smoking, drug use and kind of protective equipment (p<0.1). 3. Genetic polymorphism of CYP2E1 and ALDH2 did not affect urinary methylhippuric acid level in the exposed group (p>0.05). Conclusions : Exposure grade, smoking, drug use and kind of protective equipment affected urinary methylhippuric acid level, whereas genetic polymorphism of CYP2E1 and ALDH2 did not. However, further investigation for the effect of genetic polymorphism on the metabolism of xylene with a larger sample size is needed.

일부 조선업 근로자들의 bisphenol A 노출실태와 생물학적 지표

김청식,박준호,차봉석,박종구,김헌,장성훈,고상백,Kim, Cheong-Sik,Park, Jun-Ho,Cha, Bong-Suk,Park, Jong-Ku,Kim, Heon,Chang, Soung-Hoon,Koh, Sang-Baek 대한예방의학회 2003 예방의학회지 Vol.36 No.2

용접공은 용접과정에서 용접 흄, 중금속 및 bisphenol-A에 노출된다. 따라서 이 연구는 직무노출 메트릭스에 근거하여 근로자들의 내분비 교란물질의 노출실태를 파악하고자 하였다. 또한 생물학적 모니터링에 사용되는 뇨중 대사산물 농도에 영향을 미칠 것으로 생각되는 대사효소의 유전적 다형성 분포를 조사하였으며 이들 유전자가 뇨중 대사산물 배설에 미치는 영향을 연구하고자 하였다. 연구대상자는 경상남도에 있는 모 조선업체에 종사하는 근로자를 대상으로 하였다. 연구대상자는 총 84명으로 용접공 47명과 대조군 37명을 대상으로 하였다. 이름, 연령, 보호구 착용 여부, 흡연습관, 음주여부 등에 대하여 설문조사를 시행하였다. 시료채취는 건강검진이 진행되는 오후에 하였으며 뇨중 BPA는 뇨중 크레아티닌으로 보정하여 측정하였다. 대사효소의 유전자 다형성은 혈액의 백혈구로부터 DNA를 추출하여 제한 효소 절단 단편 다형성(restriction fragment length polymorphism, RFLP)법으로 검사하였다. 흄 중 BPA의 농도는 최대값 229.9 ng/mg, 최소값 5.7 ng/mg, 평균 61.9 ng/mg 이었다. 흄 총 중량과 흄중 BPA 양 간에 상관계수는 0.516으로 양적 선형관계를 보여주었다. 뇨중 BPA 농도는 대조군보다 용접공에서 유의하게 높았다. CYP1A1, CYP2E1, UGT1A6등의 유전자 다형성에 따라 뇨중 BPA 농도에는 차이가 없었다. 뇨중 BPA에 대한 다중회귀분석에서는 노출등급만이 유의한 변수였다. 용접 흄에 노출된 후 뇨중 BPA농도에 영향을 가장 큰 영향을 미치는 것은 노출등급이었으며, 대사효소의 유전적 다형성은 유의한 효과를 나타내지 못하였다. Objectives : Because shipyard workers are involved with various manufacturing process, they are exposed to many kinds of hazardous materials. Welders especially, are exposed to bisphenol-A (BPA) during the welding and flame cutting of coated steel, This study was conducted to assess the exposure status of the endocrine disrupter based on the job-exposure matrix. The effects of the genetic polymorphism of xenobiotic enzyme metabolisms involved in the metabolism of BPA on the levels of urinary metabolite were investigated. Methods : The study population was recruited from a shipyard company in the f province. A total of 84 shipbuilding workers 47 and 37 in the exposed and control groups, respectively, were recruited for this study. The questionnaire variables included, age, sex, use of personal protective equipment, smoking, drinking and work duration. The urinary metabolite was collected in the afternoon and correction made for the urinary creatinine concentration. The of the CYP1A1, CYP2E1 and UGT1A6 genotypes were investigated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods with the DNA extracted from venous blood. Results : The urinary BPA level in the welders group was significantly higher than in the control group (p<0.05). The urinary BPA concentration with the wild type UGT1A6 was higher than the other UGT1A6 genotypes, but with no statistical significant. From themultiple regression analysis of the urinary BPA, the regression coefficient for job grade was statistically significant (p<0.05). Conclusions : The grade of exposure to BPA affected the urinary BPA concentration was statistically significant. However, the genetic polymorphisms of xenobiotics enzyme metabolism were not statistically significant. Further investigation of the genetic polymorphisms with a larger sample size is needed.

Erythrocyte Cholinesterase Activity and Demographic Factors in Healthy Human

이원진,김청식,김진석,장성훈,Lee, Won-Jin,Kim, Cheong-Sik,Kim, Jin-Seok,Chang, Soung-Hoon 한국농촌의학.지역보건학회 2000 농촌의학·지역보건 Vol.25 No.1

적혈구 콜린에스테라제 활성도와 성, 연령, 키, 몸무게, 음주 및 흡연력 등 인구학적 특성과의 관련성을 살펴보기 위해서, 두 곳의 농약 사업장 근로자 52명과 의과대학생 51명 등 총 103명을 대상으로 현장 검사용 기계를 이용해 2000년 1월부터 2월까지 적혈구 콜린에스테라제 활성도를 측정하였다. 조사 대상자는 남성이 89명(86.4%), 여성이 14명(13.6%)였으며 평균 연령은 각각 $31.8{\pm}11.4$, $27.1{\pm}10.1$ 세였다. 측정된 적혈구 콜리에스테라제 활성도의 평균값은 남성에서 $34.7{\pm}3.9$ U/g hemoglobin, 여성에서 $34.0{\pm}4.0$ U/g hemoglobin으로 군간 유의한 차이가 없었다. 한편 적혈구 콜린에스테라제 활성도와 조사된 모든 인구학적 변수들간에는 유의하지 않은 매우 낮은 상관성만이 관찰되었다. 결론적으로 적혈구 콜린에스테라제 활성도는 혈장 콜린에스테라제 활성도와는 달리 성, 연령, 키, 몸무게 등 인구학적 변수와 상관성을 보이지 않는다고 판단되었다.

연 폭로 근로자들의 지질과산화 및 항산화상태에 관한 연구

이원진,황천현,김청식,장성훈,김양호,김해준,Lee, Won-Jin,Hwang, Cheon-Hyun,Kim, Cheong-Sik,Chang, Soung-Hoon,Kim, Yang-Ho,Kim, Hae-Joon 대한예방의학회 1998 Journal of Preventive Medicine and Public Health Vol.31 No.3

This study was started to find out if plasma malondialdehyde(MDA), $\alpha-tocopherol$ and erythrocyte superoxide dismutase(SOD) activity could be markers of biological activity resulting from exposed to lead in workers. Blood samples were randomly obtained from lead-exposed workers(n=29), $CO_2$, welders(n=60) and office workers(n=60). We used whole blood to analyse blood lead with atomic absorption spectrophotometer. Superoxide dismutase activity in erythrocyte was measured with spetrophotometer. MDA and $\alpha-tocopherol$ in plasma were measured with high performance liquid chromatography. Lead-exposed workers was significantly high in blood lead concentration$(29.37{\mu}g/d\ell)$ compared with welders$(6.42{\mu}g/d\ell)$ and office workers$(5.01{\mu}g/d\ell)$. The level of plasma MDA was significantly higher in the lead-exposed workers($1.87{\mu}mol/g$ cholesterol) than the welders($1.41{\mu}mol/g$ cholesterol) and office workers($1.41{\mu}mol/g$ cholesterol). Erythrocyte SOD activity in lead-exposed workers(56.80 U/g Hb) was significantly increased than those of welders(37.63 U/g Hb) and office workers(20.47 U/g Hb). The plasma $\alpha-tocopherol$ level of lead-exposed workers($4.93{\mu}g/g$ cholesterol) was statistically different from welders($4.25{\mu}g/g$ cholesterol) and office workers$4.28{\mu}g/g$ cholesterol). Neither age nor smoking was related to SOD or MDA level. Blood lead was significantly correlated with erythrocyte SOD activity(r=0.405), plasma MDA(r=0.296) and $\alpha-tocopherol$ (r=0.207). Plasma MDA was also significantly correlated with SOD (r=0.217). In multiple regression analysis, the change of MDA and SOD activity level related to the blood lead concentration. These results suggested that the increase of plasma MDA and erythrocyte SOD activity in lead-exposed workers had a close relationship with the oxidative stress induced by lead.

일부 농촌주민에서 Alcohol Use Disorders Identification Test를 이용한 위험 및 유해 음주율 조사

김형수,이건세,김청식,김기옥,장성훈,Kim, Hyeong-Su,Lee, Kun-Sei,Kim, Cheong-Sik,Kim, Ki-Ock,Chang, Soung-Hoon 대한예방의학회 2001 예방의학회지 Vol.34 No.3

Objectives : To investigate the prevalence of hazardous and harmful alcohol use, which are a subthreshold of alcohol related disorders, Methods : Direct-interview questionnaires to 1,183 rural persons (489 male, 694 female) were conducted in Chungju-city from July 2 to 20, 1998. As a screening instrument, the alcohol use disorders identification test (AUDIT) was used. Results : The prevalence of alcohol use was 41.7%. In males, it was 66.3% and in females, it was 24.4%. The mean of the AUDIT score of males and females was 13.2 and 5.6, respectively. As WHO guideline, the prevalence of hazardous alcohol use in males and females was 80.3% and 20.7%, respectively. This suggests that the prevalence of 'hazardous drinking' and 'harmful drinking' was 45.4% and 29.3% for males and 1.2% and 2.4% for females, respectively. Conclusions : This study presented the prevalence of hazardous and harmful drinking of a rural population in Korea and reviewed those health problems. Further evaluation to detect and treat lower alcoholic drinkers is recommended.

한국인 다기관 암 코호트 시료의 DNA 생활성도 평가

양미희,유지현,김청식,신애선,강대희,장성훈,박수경,신해림,유근영,Yang, Mi-Hi,Yoo, Ji-Hyun,Kim, Cheong-Sik,Shin, Ae-Sun,Kang, Dae-Hee,Chang, Soung-Hoon,Park, Sue-Kyung,Shin, Hai-Rim,Yoo, Keun-Young 대한예방의학회 2003 예방의학회지 Vol.36 No.4

Objectives : Peripheral blood-buffy coat fractions (N=14,956) have been stored at $-70^{\circ}C$ in the headquarter of the Korean Multicenter Cancer Cohort (KMCC), since 1993. To study the future molecular etiology of cancers using specimens of the cohort, properly stored specimens are necessary, Therefore, the DNA-viability of the bully coat samples was investigated. Methods : Buffy coat fraction samples were randomly selected from various collection areas and years (N=100). The DNA viability was evaluate from the UV-absorbent ratios at 260/280nm and the PCH for $\beta$-globin was performed with genomic DNA isolated from the buffy coat. Results : PCR products were obtained from 85 and 98% of the C and H area-samples, respectively, using 50 or $100{\mu}l$ of the buffy coat. There were significant differences in the yields of the PCR-amplifications from the C and H areas (p<0.05), which was due to differences in the homogenization of the buffy coat fractions available as aliquots. The PCR-products were obtained from all of the samples (N=7) stored at the C area-local confer, but the other aliquots stored at the headquarter were not PCR-amplified, Therefore, the PCR products in almost all the samples, even including the DNA-degraded samples, were obtained. In addition, an improvement in the DNA isolation, i,e. approx. 1.6 fold, was found after using extra RBC lysis buffer. Conclusions : PCR products for $\beta$-globin were obtained from nearly all of the samples. The regional differences in the PCR amplifications were thought to have originated from the different sample-preparation and homogenization performance. Therefore, the long term-stored buffy coat species at the KMCC can be used for future molecular studies.

Erythrocyte Cholinesterase Activity and Demographic Factors in Healthy Human

Won-Jin Lee(이원진),Cheong-Sik Kim(김청식),Jin-Seok Kim(김진석),Soung-Hoon Chang(장성훈) 한국농촌의학 지역보건학회 2000 농촌의학·지역보건 Vol.25 No.1

1996년도 의학과 평가에 사용된 정량적 평가항목들의 타당도 분석

장성훈(Soung-Hoon Chang),이원진(Won-Jin Lee),이건세(Kun-Sei Lee),김청식(Cheong-Sik Kim),김상윤(Sang-Yoon Kim) 한국의학교육학회 1999 Korean journal of medical education Vol.11 No.2

1996년에 시행한 의학과 평가에서 사용한 평가지표 중에서 정량적인 평가지표들을 대상으로 각 지표의 자료와 평가 결과를 비교 분석하였다. 조사에 사용된 자료는 한국의과대학장협의회에서 발간하고 있는 의과대학교육현황의 자료를 사용하였다. 평가 결과에서 우수 대학으로 판정된 군의 자료가 다른 군의 자료와 통계적으로 가장 의미 있는 차이를 보인 정량적 평가 지표는 기초의학 교수 및 조교의 숫자이었으며, 연구실적, 대학원 학생수, 도서관 장서 및 교육 공간도 우수대학 군이 잘 확보하고 있는 것으로 분석되어 타당성 있는 평가지표로 판단되었다. 의학과 학생수는 평가 결과와 잘 연계되었지만 국내 의학과의 평가 지표로서는 부적절하며 다른 평가지표들은 평가 결과에 영향을 줄 정도의 차이는 없었다고 판단되었다. The purpose of this study is to review the validity of quantitative indices on the Evaluation of Korean Medical Schools in 1996. The data required for the indices were obtained from the 1996 s edition of the Directory of Korea Medical Education and compared to the results of the evaluation. Among the quantitative indices of the evaluation the number of professors and assistants of basic medical science was the most valuable index to differentiate the better group from lesser groups of medical schools in Korea.

시판 청량음료 시음 후의 마뇨산 배설에 관한 실험적 연구

장성훈,김청식,김준식 건국대학교 의과학연구소 1999 건국의과학학술지 Vol.9 No.-

In this study, we measured the urinary excretion of the hippuric acid after ingestion of several kinds of common soft drinks. The urinary hippuric acid has been known as a sensitive and specific biomarker of toluene exposure in workplace. But it has not been known exactly that drinking some kinds of soft drinks can increase urinary hippuric acid significantly even in usual dosage. These phenomena surely can invoke problems in interpretation of urinary hippuric acid at the regular health check up of the workers exposed to toluene. We recruited 140 healthy volunteers(medical school students) and surveyed their diet history, medication, smoking and drinking habit before experiment. The persons who had eaten some kinds of food or drinks which were including benzoic acid were excluded and the rest 122 were divided into 2 groups. The Experimental group(n=88) drank the soft drinks which contained benzoic acid, and the control group(n=34) drank the soft drinks which contained not. We checked the excretion of urinary hippuric acid in 1.5hr and 3hr after ingestion of the drinks in each group. The measurement of urinary hippuric acid was performed by using high performance liquid chromatography(HPLC). The results were as follows: 1. The mean age(year) was 23.3±1.4 in experimental group, and 23.5±2.4 in control group; the number of female was 13(14.8%) and 4(11.8%) in each group. 2. The geometric mean of urinary hippuric acid before drinking soft drinks was 0.24, and 0.21g/l in experimental and control group(p=0.426). In 1.5 hour after ingestion of the drinks, the geometric mean increased 1.14g/l in experimental group, and 0.17g/l in control group, which was significantly different after adjusting the urinary hippuric acid before drinking(p<0.01). By addition some other covariates(sex, smoking in amount) in the model, the result was not changed(p<0.01). In 3.0 hour after ingestion, the geometric mean was 0.32 and 0.16g/l in each group, even the difference was much smaller than that of 1.5 hour after drinking, which was statistically different after adjusting the urinary hippuric acid of before drinking(p<0.01), sex and smoking additionally(p<0.01). 3. The mean increasement of urinary hippuric acid after 1.5 hour(Diff 1) after ingestion was 0.83 in experimental group, which was significantly different from that of control group(-0.06, p<0.01). Diff 2(the increasement after 3.0 hour) was also different from each other(p<0.01). 4. We used 7 different kinds of soft drinks in experimental group. The increasement after drinking them was different from 0.57 to 1.05g/l after 1.5 hour, from -0.08 to 0.08g/l after 3.0 hour, but statistically not significant in each other(p=0.146, p=0.849 in sequence). We concluded that the soft drinks which contain benzoic acid could increase the urinary hippuric acid excretion significantly, even over 1.0g/l without toluene exposure. It seems to be needed that check the diet and drink(at least 3.0 hour before collect the urine) history is essential in interpretation of urinary hippuric acid concentration.

일부 농약 취급 근로자들의 성호르몬 상태

이원진,김청식,김형수,이창훈,김진석 대한산업의학회 2000 대한직업환경의학회지 Vol.12 No.2

Objective : This study was carried out to determine the effects of occupational pesticides exposure on the level of serum Luteinizing Hormone (LH), Follicle Stimulating Hormone (FSH), testosterone in male workers. Methods : Twenty-two male workers exposed to pesticides were compared with twenty-eight male workers at same factory who were not exposed to pesticides. The selected variables for studying reproductive hormones were LH, FSH and testosterone. As part of the baseline health status, subjects were asked medical history. Results : There were no statistically significant differences on the level of LH, FSH, testosterone between the exposed and non-exposed group. Also the level of sex hormones were not significant difference with each department in exposed group. And the level of LH, FSH positively correlated with age. Conclusions : These results indicate that there are no alterations in LH, FSH, testosterone at workers exposed to pesticides. But our findings are highly preliminary because of a small sample size. Thus it calls for furthur investigation of the hormonal effects at workers exposed to pesticides.