內源性亞硝胺在食管癌一級預防中的作用及意義_West China Medical Journal

Authors：

鄭希 , 胡楊 , 袁勇 ,  趙雍凡

Corresponding?author：

趙雍凡, Email: zheng.xi@foxmail.com

Keywords：

內源性亞硝胺; 食管癌; 一級預防

DOI：

10.7507/1002-0179.20130615

Video：

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亞硝胺是一類公認的食管癌化學致癌物。它們廣泛存在于人類生存環境中（外源性亞硝胺），也可在一定條件下于人體內合成（內源性亞硝胺）。我國通過控制人群外源性亞硝胺暴露的措施，并未使食管癌發病率明顯下降，故內源性亞硝胺誘發人類食管癌的作用可能強于外源性亞硝胺。內源性合成是人體亞硝胺的主要來源，且內源性亞硝胺可致人類食管癌，因而減少人體內源性亞硝胺的暴露可成為食管癌一級預防的重要措施。關于內源性亞硝胺與食管癌預防的可能研究方向總結如下：① 減少亞硝胺底物的攝入及形成、抑制亞硝胺合成反應可減少內源性亞硝胺的暴露;② 亞硝胺在體內的吸收過程可能為被動擴散，干預其吸收過程仍存在困難;③ 亞硝胺本身不致突變，其致突變活性決定于其在體內的代謝或誘導產物，故抑制亞硝胺體內代謝活化也可能抑制食管癌的發生。

Citation： 鄭希,胡楊,袁勇,趙雍凡. 內源性亞硝胺在食管癌一級預防中的作用及意義. West China Medical Journal, 2013, 28(12): 1945-1948. doi: 10.7507/1002-0179.20130615 Copy

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2.	Jakszyn P, Gonzalez CA. Nitrosamine and related food intake and gastric and oesophageal cancer risk: a systematic review of the epidemiological evidence[J]. World J Gastroenterol, 2006, 12(27): 4296-4303.
3.	Mao WM, Zheng WH, Ling ZQ . Epidemiologic risk factors for esophageal cancer development[J]. Asian Pac J Cancer Prev, 2011, 12(10): 2461-2466.
4.	Wilp J, Zwickenpflug W, Richter E. Nitrosation of dietary myosmine as risk factor of human cancer[J]. Food Chem Toxicol, 2002, 40(8): 1223-1228.
5.	Lambert R, Hainaut P. The multidisciplinary management of gastrointestinal cancer. Epidemiology of oesophagogastric cancer[J]. Best Pract Res Clin Gastroenterol, 2007, 21(6): 921-945.
6.	Lijinsky W. Reaction of drugs with nitrous acid as a source of carcinogenic nitrosamines[J]. Cancer Res, 1974, 34(1): 255-258.
7.	Xie TP, Zhao YF, Chen LQ, et al. Long-term exposure to Sodium nitrite and risk of esophageal carcinoma: a cohort study for 30 years[J]. Dis Esophagus, 2011, 24(1): 30-32.
8.	Huang YG, Ji JD, Hou QN. A study on carcinogenesis of endogenous nitrite and nitrosamine, and prevention of cancer[J]. Mutat Res, 1996, 358(1): 7-14.
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10.	Al Bulushi I, Poole S, Deeth HC, et al. Biogenic amines in fish: roles in intoxication, spoilage, and nitrosamine formation-a review[J]. Crit Rev Food Sci Nutr, 2009, 49(4): 369-377.
11.	夏登勝, 王松靈. 唾液硝酸鹽、亞硝酸鹽代謝及其對人體影響的研究[J]. 北京口腔醫學, 2005, 13(1): 57-59.
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13.	Reed PI, Smith PL, Haines K, et al. Effect of cimetidine on gastric juice N-nitrosamine concentration[J]. Lancet, 1981, 2(8246): 553-556.
14.	Ziebarth D, Spiegelhalder B, Bartsch H. N-nitrosation of medicinal drugs catalysed by bacteria from human saliva and gastro-intestinal tract, including Helicobacter pylori[J]. Carcinogenesis, 1997, 18(2): 383-389.
15.	Kapil V, Haydar SM, Pearl V, et al. Physiological role for nitrate-reducing oral bacteria in blood pressure control[J]. Free Radic Biol Med, 2013, 55: 93-100.
16.	Waddell WJ. Critique of dose response in carcinogenesis[J]. Hum Exp Toxicol, 2006, 25(7): 413-436.
17.	Waddell WJ, Fukushima S, Williams GM. Concordance of thresholds for carcinogenicity of N-nitrosodiethylamine[J]. Arch Toxicol, 2006, 80(6): 305-309.
18.	Abrams JA, Gonsalves L, Neugut AI. Diverging trends in the incidence of reflux-related and Helicobacter pylori-related gastric cardia cancer[J]. J Clin Gastroenterol, 2013, 47(4): 322-327.
19.	Silva JF, Bidinotto LT, Furtado KS, et al. Maté attenuates DNA damage and carcinogenesis induced by diethylnitrosamine and thermal injury in rat esophagus[J]. Food Chem Toxicol, 2009, 47(7): 1521-1529.
20.	Maliakal P, Sankpal UT, Basha R, et al. Relevance of drug metabolizing enzyme activity modulation by tea polyphenols in the inhibition of esophageal tumorigenesis[J]. Med Chem, 2011, 7(5): 480-487.
21.	Yang H, Fang J, Jia X, et al. Chemopreventive effects of early-stage and late-stage supplementation of vitamin E and Selenium on esophageal carcinogenesis in rats maintained on a low vitamin E/Selenium diet[J]. Carcinogenesis, 2011, 32(3): 381-388.
22.	Pegg AE, Perry W. Alkylation of nucleic acids and metabolism of small doses of dimethylnitrosamine in the rat[J]. Cancer Res, 1981, 41(8): 3128-3132.
23.	Haorah J, Miller DW, Brand R, et al. Diffusion of dialkylnitrosamines into the rat esophagus as a factor in esophageal carcinogenesis[J]. Carcinogenesis, 1999, 20(5): 825-836.
24.	Lundberg JO, Weitzberg E. Biology of nitrogen oxides in the gastrointestinal tract[J]. Gut, 2013, 62(4): 616-629.
25.	de Castro Junior MA, Kruel CD, Meurer L, et al. Immunohistochemical expression of P53 and Ki-67 in diethylnitrosamine-induced carcinomas esophageal: experimental model[J]. Rev Col Bras Cir, 2010, 37(2): 128-134.
26.	Hebels DG, Briedé JJ, Khampang R, et al. Radical mechanisms in nitrosamine-and nitrosamide-induced whole-genome gene expression modulations in Caco-2 cells[J]. Toxicol Sci, 2010, 116(1): 194-205.
27.	Chen T, Stoner GD. Inducible nitric oxide synthase expression in N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis[J]. Mol Carcinog, 2004, 40(4): 232-240.
28.	Gomez MI, Swann PF, Magee PN. The absorption and metabolism in rats of small oral doses of dimethylnitrosamine. Implication for the possible hazard of dimethylnitrosamine in human food[J]. Biochem J, 1977, 164(3): 497-500.
29.	Yang CS, Smith T, Ishizaki, et al. Enzyme mechanisms in the metabolism of nitrosamines[J]. IARC Sci Publ, 1991(105): 265-274.
30.	Huang Q, Stoner G, Resau J, et al. Metabolism of N-nitrosomethyl-n-amylamine by microsomes from human and rat esophagus[J]. Cancer Res, 1992, 52(13): 3547-3551.
31.	Chowdhury G, Calcutt MW, Nagy LD, et al. Oxidation of methyl and ethyl nitrosamines by cytochrome P450 2E1 and 2B1[J]. Biochemistry, 2012, 51(50): 9995-10007.
32.	Loeppky RN. The mechanism of bioactivation of N-nitrosodiethanolamine[J]. Drug Metab Rev, 1999, 31(1): 175-193.
33.	Chen T, Hwang H, Rose ME, et al. Chemopreventive properties of black raspberries in N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis: down-regulation of cyclooxygenase-2, inducible nitric oxide synthase, and c-Jun[J]. Cancer Res, 2006, 66(5): 2853-2859.
34.	Stoner GD, Chen T, Kresty LA, et al. Protection against esophageal cancer in rodents with lyophilized berries: potential mechanisms[J]. Nutr Cancer, 2006, 54(1): 33-46.
35.	Stoner GD, Wang LS, Seguin C, et al. Multiple berry types prevent N-nitrosomethylbenzylamine-induced esophageal cancer in rats[J]. Pharm Res, 2010, 27(6): 1138-1145.

1. 　Craddock VM. Aetiology of oesophageal cancer: some operative factors[J]. Eur J Cancer Prev, 1992, 1(2): 89-103.
2. 　Jakszyn P, Gonzalez CA. Nitrosamine and related food intake and gastric and oesophageal cancer risk: a systematic review of the epidemiological evidence[J]. World J Gastroenterol, 2006, 12(27): 4296-4303.
3. 　Mao WM, Zheng WH, Ling ZQ . Epidemiologic risk factors for esophageal cancer development[J]. Asian Pac J Cancer Prev, 2011, 12(10): 2461-2466.
4. 　Wilp J, Zwickenpflug W, Richter E. Nitrosation of dietary myosmine as risk factor of human cancer[J]. Food Chem Toxicol, 2002, 40(8): 1223-1228.
5. 　Lambert R, Hainaut P. The multidisciplinary management of gastrointestinal cancer. Epidemiology of oesophagogastric cancer[J]. Best Pract Res Clin Gastroenterol, 2007, 21(6): 921-945.
6. 　Lijinsky W. Reaction of drugs with nitrous acid as a source of carcinogenic nitrosamines[J]. Cancer Res, 1974, 34(1): 255-258.
7. 　Xie TP, Zhao YF, Chen LQ, et al. Long-term exposure to Sodium nitrite and risk of esophageal carcinoma: a cohort study for 30 years[J]. Dis Esophagus, 2011, 24(1): 30-32.
8. 　Huang YG, Ji JD, Hou QN. A study on carcinogenesis of endogenous nitrite and nitrosamine, and prevention of cancer[J]. Mutat Res, 1996, 358(1): 7-14.
9. 　Rostkowska K, Zwierz K, Ró?ański A. Formation and metabolism of N-Nitrosamines[J]. Polish J Envir Stud, 1998, 7(6): 321-325.
10. 　Al Bulushi I, Poole S, Deeth HC, et al. Biogenic amines in fish: roles in intoxication, spoilage, and nitrosamine formation-a review[J]. Crit Rev Food Sci Nutr, 2009, 49(4): 369-377.
11. 　夏登勝, 王松靈. 唾液硝酸鹽、亞硝酸鹽代謝及其對人體影響的研究[J]. 北京口腔醫學, 2005, 13(1): 57-59.
12. 　Mirvish SS. Role of N-nitroso compounds (NOC) and N-nitrosation in etiology of gastric, esophageal, nasopharyngeal and bladder cancer and contribution to cancer of known exposures to NOC[J]. Cancer Lett, 1995, 93(1): 17-48.
13. 　Reed PI, Smith PL, Haines K, et al. Effect of cimetidine on gastric juice N-nitrosamine concentration[J]. Lancet, 1981, 2(8246): 553-556.
14. 　Ziebarth D, Spiegelhalder B, Bartsch H. N-nitrosation of medicinal drugs catalysed by bacteria from human saliva and gastro-intestinal tract, including Helicobacter pylori[J]. Carcinogenesis, 1997, 18(2): 383-389.
15. 　Kapil V, Haydar SM, Pearl V, et al. Physiological role for nitrate-reducing oral bacteria in blood pressure control[J]. Free Radic Biol Med, 2013, 55: 93-100.
16. 　Waddell WJ. Critique of dose response in carcinogenesis[J]. Hum Exp Toxicol, 2006, 25(7): 413-436.
17. 　Waddell WJ, Fukushima S, Williams GM. Concordance of thresholds for carcinogenicity of N-nitrosodiethylamine[J]. Arch Toxicol, 2006, 80(6): 305-309.
18. 　Abrams JA, Gonsalves L, Neugut AI. Diverging trends in the incidence of reflux-related and Helicobacter pylori-related gastric cardia cancer[J]. J Clin Gastroenterol, 2013, 47(4): 322-327.
19. 　Silva JF, Bidinotto LT, Furtado KS, et al. Maté attenuates DNA damage and carcinogenesis induced by diethylnitrosamine and thermal injury in rat esophagus[J]. Food Chem Toxicol, 2009, 47(7): 1521-1529.
20. 　Maliakal P, Sankpal UT, Basha R, et al. Relevance of drug metabolizing enzyme activity modulation by tea polyphenols in the inhibition of esophageal tumorigenesis[J]. Med Chem, 2011, 7(5): 480-487.
21. 　Yang H, Fang J, Jia X, et al. Chemopreventive effects of early-stage and late-stage supplementation of vitamin E and Selenium on esophageal carcinogenesis in rats maintained on a low vitamin E/Selenium diet[J]. Carcinogenesis, 2011, 32(3): 381-388.
22. 　Pegg AE, Perry W. Alkylation of nucleic acids and metabolism of small doses of dimethylnitrosamine in the rat[J]. Cancer Res, 1981, 41(8): 3128-3132.
23. 　Haorah J, Miller DW, Brand R, et al. Diffusion of dialkylnitrosamines into the rat esophagus as a factor in esophageal carcinogenesis[J]. Carcinogenesis, 1999, 20(5): 825-836.
24. 　Lundberg JO, Weitzberg E. Biology of nitrogen oxides in the gastrointestinal tract[J]. Gut, 2013, 62(4): 616-629.
25. 　de Castro Junior MA, Kruel CD, Meurer L, et al. Immunohistochemical expression of P53 and Ki-67 in diethylnitrosamine-induced carcinomas esophageal: experimental model[J]. Rev Col Bras Cir, 2010, 37(2): 128-134.
26. 　Hebels DG, Briedé JJ, Khampang R, et al. Radical mechanisms in nitrosamine-and nitrosamide-induced whole-genome gene expression modulations in Caco-2 cells[J]. Toxicol Sci, 2010, 116(1): 194-205.
27. 　Chen T, Stoner GD. Inducible nitric oxide synthase expression in N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis[J]. Mol Carcinog, 2004, 40(4): 232-240.
28. 　Gomez MI, Swann PF, Magee PN. The absorption and metabolism in rats of small oral doses of dimethylnitrosamine. Implication for the possible hazard of dimethylnitrosamine in human food[J]. Biochem J, 1977, 164(3): 497-500.
29. 　Yang CS, Smith T, Ishizaki, et al. Enzyme mechanisms in the metabolism of nitrosamines[J]. IARC Sci Publ, 1991(105): 265-274.
30. 　Huang Q, Stoner G, Resau J, et al. Metabolism of N-nitrosomethyl-n-amylamine by microsomes from human and rat esophagus[J]. Cancer Res, 1992, 52(13): 3547-3551.
31. 　Chowdhury G, Calcutt MW, Nagy LD, et al. Oxidation of methyl and ethyl nitrosamines by cytochrome P450 2E1 and 2B1[J]. Biochemistry, 2012, 51(50): 9995-10007.
32. 　Loeppky RN. The mechanism of bioactivation of N-nitrosodiethanolamine[J]. Drug Metab Rev, 1999, 31(1): 175-193.
33. 　Chen T, Hwang H, Rose ME, et al. Chemopreventive properties of black raspberries in N-nitrosomethylbenzylamine-induced rat esophageal tumorigenesis: down-regulation of cyclooxygenase-2, inducible nitric oxide synthase, and c-Jun[J]. Cancer Res, 2006, 66(5): 2853-2859.
34. 　Stoner GD, Chen T, Kresty LA, et al. Protection against esophageal cancer in rodents with lyophilized berries: potential mechanisms[J]. Nutr Cancer, 2006, 54(1): 33-46.
35. 　Stoner GD, Wang LS, Seguin C, et al. Multiple berry types prevent N-nitrosomethylbenzylamine-induced esophageal cancer in rats[J]. Pharm Res, 2010, 27(6): 1138-1145.

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內源性亞硝胺在食管癌一級預防中的作用及意義

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