**9. N-nitroso compounds**

Exposure to N-nitroso compounds (NOCs) is clearly related to development and increased mortality of gastric cancer (**Figure 6**) [99, 100]. It has been established that nitrogenous constituents of gastric juice can be reduced and lead to the *in situ* formation of N-nitroso compounds [101] although the involvement of *H. pylori* in the development of NOCs and premalignant lesions was controversial until recently [102]. Gastric epithelial cells exposed to N-Nitroso compounds (NOCs) such as MNNG (N-methyl-N-nitro-N-nitrosoguanidine), N-nitrosodimetilamine, N-nitroso-N-ethylurea, or N-nitrosopiperidine through diet (bacon, smoked fish, sausages), high salt consumption, alcoholic beverages, and/or tobacco smoke2 , which also contains NOCs and favors the prevalence of *H. pylori* [103], induce

#### **Figure 6.**

*Structure of relevant N-nitrosamine carcinogenic compounds. From NTP (National Toxicology Program), NIH, USA, 2014.*

<sup>2</sup> For a complete list of NOCs compounds go to http://ntp. niehs.nih.gov/pubhealth/ roc/roc13

the expression of epithelial-mesenchymal transition markers in the presence of CagA positive *H. pylori* strains [104] which is mediated by Akt or ERK activation [105], both of which are involved in tight junction assembly [28]. N-etil-N-nitro-N-nitrosoguanidine, a compound that behaves similar to MNNG [106] and induces gastric carcinoma in nonhuman primates [107], synergizes with *H. pylori*, especially CagA+ strains [108] and induces gastric carcinogenesis [109]. Therefore, protagonism of these compounds in individuals with *H. pylori* infection cannot be belittled.
