N-nitrosopiperidina y N-nitrosodibutilamina (II): relevancia en la carcinógenesis química y genotoxicidad

Abstract

N-nitrosopiperidine (NPIP) and N-nitrosodibutylamine (NDBA) have been classified as possibly carcinogenic to humans. NPIP causes tumours in oesophagus, and also in nasal cavity, liver and stomach, whereas NDBA is a bladder carcinogen. Both N-nitrosamines are considered indirect genotoxic carcinogens since they need a bioactivation to generate metabolites that react with DNA. The main DNA lesion induced by N nitrosamines is the alkylative damage. In the case of NDBA, the alkylation position is in O6 of guanine, forming O6 butylguanine and O6-4-hydroxybutylguanine. However, this N-nitrosamine alkylates proteins preferably. On the other hand, NPIP bioactivation generates metabolites that react with N2 of guanine in vitro, although its in vivo effects are unknown. Moreover, during metabolic activation reactive oxygen species (ROS) and nitrogen species (RNS) can be also produced. The most common oxidative and nitrative lesions are 8-hydroxydeoxyguanosine (8-OhdG) and 8-nitroguanine, respectively, that produce mutations and lead to carcinogenesis.