A comprehensive review on various carcinogenic aspects of N-nitrosopiperidine (NPIP)

Abstract

N-nitrosamines, the potential hazardous pollutants, are classified as most mutagenic and probable carcinogenic compounds. One of the Potentially carcinogenic N-nitroso compounds is N-nitrosopiperidine (NPIP) which is produced by the oxidation or nitrosation of amine precursors. NPIP can be found in a variety of matrices including latex products, agricultural chemicals, cosmetic items, chlorinated water, alcoholic beverages, spices, and food products. Various physical (ionized radiation, and ultraviolet light), chemical (outdoor and indoor air pollution, second-hand smoke, asbestos, metals, and vinyl chloride), and biological (diet, physical activity, infection, mutagenic and carcinogenic compounds, nitrosamines) factors are identified as precursors associated with the formation of NPIP. In addition, various genetic factors (cell cycle genes, tissue organization genes, signal transduction genes, and DNA repair genes) are also involved in the development of NPIP-directed diseases. Under physiological conditions, NPIP is found to be stable but require cytochrome P450-directed hydroxylation at the carbon atoms adjacent to nitroso group to form α-hydroxy NPIP ester for their metabolic activation. Various acute, chronic, reproductive health hazards may produce after the reaction of α-acetoxy-N-nitrosopiperidine with 2′-deoxy guanosine which can last for months or years. Different types of cancers such as esophageal, hepatocellular, pulmonary, bronchial and alveologenic are induced in response of NPIP in different animal models at 33 or 66 mg/kg, 0.88 × 10^–3 M, 0.2 mmol/kg of dosage. Tumours, such as tonofibrils, desmosomes, irregular nuclei, aggregated condensed chromatin with pars amorpha and fibrillar components, induced in lab animals show resemblance with their human counterparts with respect to their histological studies. Various studies have explored the role of food mutagen NPIP in generating caspase directed apoptosis. Apoptosis is well characterized by nucleus fragmentation, chromatin condensation, cell volume reduction, cytoplasmic shrinkage, and membrane blebbing. The safety and health organizations have taken various preventive measures to limit the exposure of NPIP carcinogenic compounds around residential areas and workplaces but this further requires population-based intervention and some policy implementation. Removal techniques like biological denitrifications, electrodialysis, ion-exchange chromatography, reverse osmosis, cellulose nanopaper membrane, etc., have also been applied to control the exposure of NPIP. Thus, NPIP has a role as an environmental pollutant, a mutagen, an apoptosis inducer, and a carcinogenic agent. Therefore, we have reviewed some basic features of NPIP and its contribution towards various types of cancers, along with some preventive measures and removal techniques of NPIP for the first time in this report.

Graphical abstract