Gut：脂肪使维生素C促进特定致癌物质形成

   根据最近发表在刊物《内脏》（Gut）上的结果，胃部的脂肪将使得维生素C促进而非抑制特定致癌物质的形成。  

    科学家们同时分析了脂肪（油脂）和维生素C（抗坏血酸）对胃下部亚硝酸盐化学物质的作用，胃下部是最容易发生癌变和肿瘤生长的区域。

    亚硝酸盐存在于人类的唾液和某些特定食物保护剂中，它们能转化为致癌物质亚硝胺。亚硝胺主要在酸性环境中形成，例如胃酸条件下。但是维生素C可以通过将亚硝酸盐转化为一氧化氮而阻碍以上过程的发生。当脂肪不存在时，维生素C将抑制两种亚硝胺的生成，抑制因子达到5－1000之间；而对于另外两种亚硝胺，维生素C则将起到完全消除的作用。  

    但是当环境中存在10%的脂肪时，维生素C将起到促进亚硝酸盐生成的作用，促进的效率在8－140倍之间。  

    文章作者表示，脂肪在进食之后将在胃的下部存在一段时间，并且它们也是构成胃内表面细胞的组成成分之一。当维生素C在酸性环境下和亚硝酸盐反应时就将生成一氧化氮。但是生成的一氧化氮能扩散到脂肪中，然后通过和氧气反应而形成能产生亚硝胺的化学物质。  

    因此作者认为，以上发现或许能说明为什么最近一些研究观察到摄入维生素C并不能降低癌症风险。

    原文链接：http://www.physorg.com/news108094911.html

原始出处:

Gut. Published Online First: 4 September 2007. doi:10.1136/gut.2007.128587

Fat transforms ascorbic acid from inhibiting to promoting acid catalysed n-nitrosation

Emilie Combet 1, Stuart Paterson 2, Katsunori Iijima 2, Jack Winter 2, William Mullen 1, Alan Crozier 1, Tom Preston 3 and Kenneth E. L. McColl 1*

1 The University of Glasgow, United Kingdom
2 Western Infirmary, Glasgow, United Kingdom
3 Stable Isotope Biochemistry Laboratory, SUERC, United Kingdom

* To whom correspondence should be addressed. E-mail: k.e.l.mccoll@clinmed.gla.ac.uk .

Background: The major potential site of acid nitrosation is the proximal stomach, an anatomical site prone to a rising incidence of metaplasia and adenocarcinoma. Nitrite, a pre-carcinogen present in saliva, can be converted to nitrosating species and N-nitroso compounds by acidification at low gastric pH in the presence of thiocyanate.

Aims: To assess the effect of lipid and ascorbic acid on the nitrosative chemistry under conditions simulating the human proximal stomach.

Methods: The nitrosative chemistry was modelled in vitro by measuring the nitrosation of four secondary amines under conditions simulating the proximal stomach. The N-nitrosamines formed were measured by gas chromatography - ion-trap tandem mass spectrometry, while nitric oxide and oxygen levels were measured amperometrically.

Results: In absence of lipid, nitrosative stress was inhibited by ascorbic acid through conversion of nitrosating species to nitric oxide. Addition of ascorbic acid reduced the amount of N-nitrosodimethylamine formed by 5-fold, N-nitrosomorpholine by >1000-fold and totally prevented the formation of N-nitrosodiethylamine and N-nitrosopiperidine. In contrast, when 10% lipid was present, ascorbic acid increased the amount of N-nitrosodimethylamine, N-nitrosodiethylamine and N-nitrosopiperidine formed by approximately 8, 60 and 140-fold respectively compared to absence of ascorbic acid.

Conclusion: The presence of lipid converts ascorbic acid from inhibiting to promoting acid nitrosation. This may be explained by nitric oxide, formed by ascorbic acid in the aqueous phase, being able to regenerate nitrosating species by reacting with O2 in the lipid phase.