臺灣博碩士論文加值系統

煉焦工廠勞工常常身處於高PAHs（多環芳香族碳氫化合物; Polycyclic aromatic hydrocarbons）的環境下，其中又以爐頂工作區域的的勞工暴露量相對較高。人體在代謝PAHs過程中會產生1-hydroxypyrene（1-OHP），因此利用尿液中存在的1-OHP濃度當作PAHs代謝生物暴露指標；DNA受到傷害，在體內進行修復的過程中，會產生DNA氧化產物8-hydroxy-2-deoxyguanosine（8-OH-dG），所以8-OH-dG 可以作為人體DNA傷害程度的指標。甘胺酸氮甲基轉化酶（Glycine N-methyltransferase, GNMT），甲烯基四氫葉酸還原酶（5,10-methylenetetrahydrofolate reductase, MTHFR）與甲硫胺酸生成酶（Methionine synthase, MS）主要參與了細胞單碳循環代謝路徑（one carbon metabolism pathway），其中GNMT會與Benzo(a)pyrene（BaP）及多種PAHs結合，保護細胞，阻止BaP與DNA形成DNA鍵結物。本研究的目的為針對台灣地區某一煉焦工廠PAHs高暴露及中低暴露員工，研究GNMT及參與其代謝路徑的MTHFR與MS之基因多型性與其尿液中1-OHP及8-OH-dG代謝濃度的關係。收集217名男性煉焦工人淋巴球DNA檢體，利用TaqMan及GeneScan方法鑑定GNMT的三個基因多型性（SNP1、STRP1、INS-DEL），並利用PCR-RFLP方法分析MS A2756G、MTHFR C677T的基因型。另外收集問卷資料，並且配合之前已分析出之尿液中1-OHP與8-OHdG代謝濃度結果進行統計分析。研究結果：在初步結果直接分析尿液中1-OHP與8-OHdG濃度值時，觀察到其濃度值在高暴露組SNP1與STRP1不同基因型之間具有差異，於是再將尿液中1-OHP與8-OHdG濃度值以自然對數轉換之後，使數值較趨近於常態分佈。利用邏輯式迴歸分析觀察到，高暴露族群，STRP1基因型為B對偶基因（B/B）者，尿液中8-OHdG濃度值高於A對偶基因（A/A或A/B）者4.41倍(95%CI =1.04 - 18.81, p = 0.044)。進一步比較GNMT不同的單倍體（haplotype）基因組合之尿液中8-OHdG代謝濃度，發現高暴露GNMT SNP1 + INS-DEL + STRP1之基因型組合為C/T + INS/INS + A/A的人，濃度顯著低於C/C + INS/DEL + B/B的人（7.6 ± 7.3 ng/ml < 32.9 ± 26.8 ng/ml, p = 0.01）。綜合以上結果，推測SNP1帶有T對偶基因的人，與STRP1帶有A對偶基因的人，以及INS-DEL帶有INS對偶基因的人，GNMT是具有較高活性（promoter transcriptional activity），代謝PAHs的能力可能較佳，因此測得尿液中1-OHP濃度值較高，相對來說，8-OHdG值較低，對於DNA氧化傷害可能具有保護作用。最後在MS以及MTHFR研究上，發現MTHFR為C/C基因型的人，結合GNMT haplotype做分析的結果，尿液中8-OHdG代謝濃度有明顯減少的現象( C/C-14.5 ± 7.3 ng/ml < C/T- 60.6 ± 18.1 ng/ml, p = 0.02)。總而言之，不同的GNMT基因型個體對於DNA受到PAHs致癌性傷害上，可能具有一個保護作用，而MTHFR可能扮演一修飾基因的角色，本研究對於PAHs暴露環境之勞工安全衛生及預防醫學有所幫助。

Coke-oven workers (COWs) are occupationally exposed to high concentrations of polycyclic aromatic hydrocarbons (PAHs), especially workers near the topside of the oven. Uninary 8-hydroxy-2-deoxyquanosine (8-OH-dG) and 1-hydroxypyrene (1-OHP) are biomarkers of oxidative DNA damage and PAH metabolism, respectively. Previously, we found that glycine N-methyltransferase (GNMT) can bind benzo(a)pyrene (BaP) and inhibit DNA adducts formation. Since methionine synthase (MS), 5,10-methylene- tetrahydrofolate reductase (MTHFR) and GNMT are involved in the one-carbon metabolism pathway, we would like to study the associations of the genetic polymorphisms of these genes and the urinary biomarkers in coke-oven workers. Questionnaires and lymphocyte DNA were collected from 217 coke-oven workers which including 54 workers from the topside of the oven (high exposure group, group A) ,92 workers from both sides of the oven (medium exposure group, group B) and 71 administrative persons from the same factory (low exposure group, group C). Three genotypes of GNMT-SNP1, INT/DEL, and STRP1 were analyzed using TagMan and GeneScan methods; both A2756G genotype of MS gene and C677T genotype of MTHFR gene were analyzed using PCR-RFLP. Results：The preliminary results indicate that there is a reverse relationship between the urinary levels of 1-OHP and 8-OH-dG in the group A workers with different GNMT genotypes. Use logistic regression analysis indicated that workers with GNMT STRP1-B/B genotypes had higher 8-OHdG level than those with STRP1-A/A or A/B genotype in the group A (OR= 4.41, 95%CI =1.04-18.81, p= 0.044, respectively).For the GNMT haplotype study, workers with SNP1+INS-DEL+STRP1-C/T+INS/INS+A/A had lower 8-OHdG level than those with SNP1+INS-DEL+STRP1-C/T + INS/DEL + B/B in group A（7.6 ± 7.3 ng/ml < 32.9 ± 26.8 ng/ml, p = 0.01）. In conclusion, GNMT may have a protective effect against the exposure to carcinogens such as PAHs, and the interactions of the genetic polymorphisms of GNMT, MS, MTHFR were associated with different 1-OHP and 8-OHdG level in coke-oven workers. This study may be useful for the genetic counseling of workers who expose to environment carcinogens related to PAHs.

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盧佩玲：多環芳香族碳氫化合物暴露工人生物偵測與呼吸防護具有效防護係數研究。國立陽明大學公共衛生研究所，民國九十年。
潘致弘：鋼鐵工廠煉焦工人健康危害評估研究。行政院勞工委員會勞工安全衛生研究所，民國九十年。
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吳泰雯：冶金焦炭之製造及副產品之回收。中國鋼鐵股份有限公司。