Carcinogenicity nitrosamines

Cyclic nitrosamines are among the most potent and environmentally significant nitrosamine carcinogens. Like the acyclic nitrosamines, metabolism is necessary for their carcinogenicity. Elucidation of the specific metabolic pathways of cyclic nitrosamine activation and detoxification is a challenging problem, and considerable progress has been achieved in recent years. In this chapter, we will review metabolic studies on N-nitrosopyrrolidine (NPYR), N -nitrosonornicotine (NNN), N-nitrosopiperidine (NPIP), N-nitrosohexamethyleneimine (NHEX), N-nitrosomorpholine (NMOR),... 

Walse SS, Mitch WA (2008) Nitrosamine carcinogens also swim in chlorinated pools. Environ Sci Technol 42 1032-1037... 

Singer, G.M., Taylor, H.W., Lijinsky, W. (1977) Lipophilicity as an aspect of nitrosamine carcinogenicity quantitative correlations and qualitative observation, Chem.-Biol. Interact. 19, 133-142. 

M. Poulsen, D. Spangler, and G. H. Loew, Mol. Toxicol., 1, 35 (1987). Nitrosamine Carcinogen Activation Pathway Determined by Quantum Chemical Methods. 

Photoaddition of nitrosamines (carcinogens) to alkenes in the presence of oxygen gives quite good yields of 1 1 adducts as their oxime isomers.Nitronium tetiafluoroborate in acetonitrile adds to alkenes in Maricovnikov manner, giving acetamidonitro compounds, 38-84% (from arylalkenes) or... 

Wishnok JS, Archer MC, Edelman AS, Rand WM. Nitrosamine carcinogenicity A quantitative Hansch-Taft structure-activity relationship. Chem Biol Interact 1978 20 43-54. 

Khudoley, V.V. Use of aquarium fish, Danio rerio and Poecilia reticulata, as test species for evaluation of nitrosamine carcinogenicity. Natl Cancer Inst. Monogr. 65 65-70, 1984. 

Tsutsumi M, Masutani M, Nozaki T et al. Increased susceptibility of polyCADP-ribose) polymetase-1 knockout mice to nitrosamine carcinogenicity. Cucinogenesis 2001 22(l) l-3. 

At present, there is anxiety that nitrous acid, which people consume in cigarette smoke and in preserved meats, may be uniting with secondary amines in the stomach, to form nitrosamine carcinogens (see Section 13.5 for carcinogenesis). In this connexion, it is interesting that the molecular form is the species of secondary amines that reacts fastest with nitrous acid, so that amines that are only feebly ionized at pH 2 would be the most susceptible to nitrosamine formation (Sander, Schweinsberg and Menz, 1968). These weak amines seem to be quite uncommon in the stomach contents. 

Wishnok, J. S., Archer, M. C., Edelmann, A. S. and Rand, W. M. (1978) Nitrosamine carcinogenicity a quantitative Mansch-Taft structure-activity relationship. Chem. Biol Interact., 20, 43-54. 

Modem legislation puts much emphasis on the prevention of the formation of carcinogenic secondary iV-nitrosamines as by-products of sulfur vulcanization (30). This limits the choice of possible accelerators to those which have no secondary amine groups embedded in their chemical stmcture or may contain residual secondary amines dating back to their synthesis usually the ultra-accelerators mentioned above. In such cases it is extra difficult to develop a proper vulcanization system. New ultra-accelerator systems like dibenzyl dithiocarbamate or tetrabenzyl thiuramdisulfide may be used in such cases, where the dibenzylamine embedded in these compoimds is an exception in that it does not generate N-nitrosamines carcinogenic to human beings (31). 

---