• 作者： 林仁混
• 作者服務機構： 國立臺灣大學醫學院生化學研究所
• 中文摘要： 本綜合報告是著者近數年來，對生物界中致癌性亞硝基化合物之分佈與生體轉變加以研究，特別注重其存在與國民
  疾病之可能關連。文中介紹過去所得之結果；並進一步與其他相關之文獻加以綜合申論。
  內生性致癌物係指生體內之細胞利用攝取之前驅物質加以合成之致癌物。此處所指之前驅物質可能為無害物質。目
  前甚受重視的致癌性亞硝基化合物就是此類致癌物之代表。它們的直接前驅物質為亞硝酸鹽與二級胺；它們間接的前驅
  物質為硝酸鹽，一級胺與三級胺。硝酸鹽與亞硝酸鹽廣泛的存在於人類的環境中，人體也可以自行合成。食物中之胺類
  來源，分佈各處但其詳細含量與生體轉變，則有待進一步之研究。
  由各方面之研究結果顯示，亞硝酸鹽可經由唾液與腸管中微生物?還元硝酸鹽而得。硝酸鹽在蔬菜與飲水中含量頗
  為可觀。因此食物中胺類之含量變為形成亞硝基化合物之關鍵因素。也就是說內生性之亞硝基化合物之含量，端視攝取
  之胺類化合物含量而定。本研究室幾年來，一直進行食物中胺類化合物之探討並獲得下列之結果：
  （一）建立胺類化合物之快速定量分析法－Dabsylation-HPLC法。在以往對甲胺，乙胺，二甲胺，二乙胺等之分析，都採用
  蒸餾分析法，但由於這些胺類揮發性很高，定量不易。本研究室以首創之達佈氯（dabsyl chloride）先與胺類化合物反
  應而形成金黃色衍生物，再由HPLC來定性定量。
  （二）海產食物如魚、蝦、魷魚、蟑魚等含有高量之二甲胺，尤其乾魷魚中可高到2000 ppm以上。二甲胺之前驅物可能為
  三甲胺氧化物，它的含量可高達數萬ppm。約90％之三甲胺氧化物經加熱可轉變為三甲胺與二甲胺。
  （三）發酵釀造的產品如酒、醬油，含有低量的二甲胺。經過特殊發酵製造的黑豆鼓含有較高的胺類化合物。
  （四）白胡椒與黑胡椒都含有相當量的胡椒素（piperidine）紅辣椒不含胡椒素。胡椒素經與亞硝酸鹽作用可形成致癌性之亞
  硝基胡椒素（N-Nitrosophenacetin）。
  （五）非那西汀為常用之鎮痛藥，常期大量服用可引起腎臟疾病，甚至可引起腎癌，在酸性下，此藥物可與亞硝酸鹽反應而
  形成高活性之亞硝基非那西汀（N-nitroso-piperidine）。此新化物具有很強的致突變性與致畸型作用。
  （六）由各方面之研究顯示，人類內生性亞硝基化合物之形成與其攝取之食物有關，如何慎選食物，控制胺類前驅物質之攝
  取，將是急待研究之課題；也將是吾人日後防癌工作之重要目標。
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• 英文摘要： This paper reviews the experimental results of our research in the past several years and other relatedpapers that have been directed toward the occurrence, biotransformation and epidemiological significanceof carcinogenic N-nitroso compounds in biosphere. Endogenous carcinogens are a group of cancer-causing compounds produced in vivo from harmlessprecursors. This category has been examplified by the well-known carcinogens, N-nitroso compounds. Thesignificance of naturally occurring amines and amides as precursors of carcinogenic N-nitroso compoundsin vivo and their implication in the incidence of human cancer have been investigated and emphasized. Extremely high levels of trimethylamine-N-oxide and dimethylamine were detected in squids andother seafoods. More than 90% of trimethylamine-N-oxide were converted to dimethylamine and trimethy-lamine on pyrolysis. Low levels of dimethylamine and methylamine were also detected in the fermentedsoybean products, wines and sauces. Both dimethylamine and trimethylamine are excellent precursors ofdimethylnitrosamine. 74Several naturally occurring aromatic amines especially 2-carboline derivatives such asharman, norharman, harmaline, harmalol, harmine and harmol are mutagenic and become more mutagenicto Salmonella typhimurium after nitrosation. Appreciable amounts of piperidine were detected in thepopular spice white and black pepper powders. Under acidic condition, piperidine reacts readily with ni-trite to form carcinogenic N-nitroso-piperidine. N-Nitrosophenacetin was formed from the reaction ofnitrite with the amide drug phenacetin. This new compound showed strong mutagenicity to Salmonellatyphimurium and Sarcina lutea and strong teratogenic activity to Leghorn chicken embryos. Studies have shown that the majority of N-nitroso compounds in the body come from in vivo con-version. Most investigators believe that this endogenous pool of N-nitroso compounds may prove to be amajor exposure route in man. The presence of naturally occurring amines and amides in the diet thenbecomes one of the crucial limiting steps in the formation of endogenous N-nitroso compounds in vivo.
• 中文關鍵字： Amines; amides; N-nitroso compounds; dimethylamine; methylamine; trimehtylamine; trimethylamine-N-oxide; seafoods; piperidine; wine; sauce; nitrosation in vivo; carcinogenesis; tumors; nitrite; nitrate; N-nitrosophenacetin; mutagenicity and teratogenicity
• 英文關鍵字： --