Handbook of Vitamin C Research

Vitamin C Protects from Oxidative DNA Damage… 89Table 1. N-Nitrosamines in the diet. Carcinogenicity and occurrence(Tricker and Preussmann,1991)In 1978 the International Agengy for Research on Cancer (IARC) classified N-Nitrosodimethylamine (NDMA) as probably carcinogenic to humans (Group 2A) and N-Nitrosopyrrolidine (NPYR), N-Nitrosopiperidine (NPIP) and N-Nitrosodibutylamine(NDBA) as possibly carcinogenic to humans (Group 2B) [4]. NDMA is the most commonlyencountered volatile N-Nitrosamine in food samples and it is a potent liver, lung and kidneycarcinogen [5, 6]. NPYR and NPIP are structurally homologous cyclic N-Nitrosamines withdiffering carcinogenic activities. Comparative carcinogenicity studies of these two N-Nitrosamines in rats have shown that NPYR induces mainly liver tumours, whereas NPIP is apotent extrahepatic carcinogen inducing tumours in the esophagus and the nasal cavity [7].Finally, NDBA is a relatively selective bladder carcinogen in rats, although also inducestumours in other tissues, such as the liver, lung and oesophagus [8].N-Nitrosamines are pre-genotoxicants that can be metabolized in reactions mediated bycytochrome P450 (CYP450) phase I enzymes to give rise to the ultimate genotoxicants [9].The first activation step of N-Nitrosamines is thought to be the hydroxylation of the carbonatom located at the -position of the N-Nitroso group. The reactive intermediates of N-Nitrosamine metabolism also have the ability to alkylate nucleophilic sites of DNA [10]resulting in alcali labile adducts, which can lead the formation of basic sites and DNA strandbreaks. The metabolic activation of NDMA by CYP2E1 is shown in Figure 1.