Volatile nitrosamine levels and genotoxicity of food samples from high‐risk areas for nasopharyngeal carcinoma before and after nitrosation

Abstract

Traditional life-style, especially food habits, infection by Epstein-Barr virus (EBV) and genetic factors, have been associated with an increased risk of nasopharyngeal carcinoma (NPC). N-Nitroso compounds and other carcinogens either present in food or formed endogenously, as well as food constituents that activate EBV, have been suspected as etiological factors in NPC pathogenesis. For their characterization preserved food items, frequently consumed in NPC endemic areas in Tunisia, South China and Greenland, were sampled and screened for the presence of mutagens and volatile nitrosamines before and after nitrosation. Aqueous extracts as well as 2 organic extracts of the samples were assayed for genotoxicity in 2 Salmonella typhimurium strains and the SOS chromotest. The same extracts had previously been analyzed for volatile nitrosamines and for EBV-activating substances in Raji cells. In our study, 13 out of 16 food samples showed a weak, directly-acting genotoxicity in the SOS chromotest in at least one of the extracts, but only one sample from Greenland was found to be weakly mutagenic in Salmonella TA 98. Chemical nitrosation for 9 out of 15 samples of aqueous food extracts increased the genotoxic effect in the SOS chromotest. Levels of volatile nitrosamines were also elevated for 12 out of 15 samples; highest levels of N-nitrosodimethylamine were found in hard salted and dried fish from China (1,200 micrograms/kg) and highest N-nitrosopyrrolidine levels in a Tunisian spice (3,840 micrograms/kg). In non-nitrosated aqueous food extracts, the level of volatile nitrosamines and genotoxic activities were not correlated with the EBV-inducing activity of the same samples. After chemical nitrosation, EBV-inducing activity was decreased or showed no change and was not correlated with increases in either the genotoxicity or the nitrosamine levels. Our results suggest that EBV-activating compounds belong to a different class of substances. However, there was an association between the changes in genotoxicity and nitrosamine levels due to nitrosation.

The Enigmatic Epidemiology of Nasopharyngeal Carcinoma

“…As a result, these foods accumulate significant levels of nitrosamines, which are known carcinogens in animals (150,152,162,163). Salt-preserved fish also contains bacterial mutagens, direct genotoxins, and EBV-reactivating substances (164)(165)(166), any or all of which could also contribute to the observed association. However, there have been no prospective studies of NPC risk associations with salt-preserved fish consumption, or virtually any other environmental exposure, in endemic areas.…”

Adulthood consumption of preserved and nonpreserved vegetables and the risk of nasopharyngeal carcinoma: A systematic review

“…17 The N-nitrosamines are a large group of nitrosamine compounds with a common carcinogenic mechanism. 46 Preserved vegetables contain N-nitrosodimethylamine and other volatile N-nitroso compounds 18 having both mutagenic and carcinogenic effects in laboratory animals. [47][48][49] If nitrosamines do contribute to the etiology of NPC, the variation in nitrosamine content in preserved foods due to regional differences in preservation methods may contribute to the heterogeneity in assigning risk to preserved vegetable consumption in different geographical locations.…”

“…The preservation processes used to prepare these types of vegetables are also thought to increase the levels of carcinogenic nitrosamines, 2 such as N-nitrosodimethylamine and other volatile N-nitroso compounds. 18 On the other hand, nonpreserved vegetables contain many components that may prevent cancer, such as fiber, carotenoids, vitamin C, folate and other vitamins. 19 The few published reviews that have mentioned the relationship between preserved and nonpreserved vegetable intake and the risk of developing NPC were part of larger reviews on either the epidemiology of NPC or the effects of dietary intake on cancer risk, 2,6,19 and did not characterize the magnitude of the associations between nonpreserved and preserved vegetable intake and NPC.…”

Higher incidence of nasopharyngeal carcinoma in some regions in the world confers for interplay between genetic factors and external stimuli

“…As a result, nitrosamines are again accumulated in high amounts (42,43). Salt-dried fish also contains various mutagens, genotoxins, and EBV-reactivating substances like 2-chloro-4-methylthiobutanoic acid (CMBA) and tyramine (42)(43)(44)(45)(46). In high-incidence populations in Tunisia, South-China and Greenland, a relatively high level of volatile nitrosamine has been detected in common food items (47).…”