Tobacco-specific A-nitrosamines

Fig. 1 Formation of tobacco-specific A -nitrosamines (Hoffmann et at. 1995). iso-NNAC, 4-(methylnitrosoamino)-4-(3-pyridyl)butyric acid iso-NNAL, 4-(methylnitrosoamino)-4-(3-pyridyl)- -butanol NAB, A -nitrosoanabasine NAT, A -nitrosoanatabine NNA, 4-(methylnitro-soamino)-4-(3-pyridyl)butanal NNAL, 4-(methylnitrosoamino)-l-(3-pyridyl)-l-butanol NNK, 4-(methylnitrosoamino)-l-(3-pyridyl)-l-butanone NNN, Af -nitrosonornicotine (Note NNA is a very reactive aldehydes and has therefore never been quantified in tobacco or tobacco smoke)...

Bhide SV, Nair J, Mara GB, Nair UJ, Kameshwar Rao BV, Chakraborty MK, Brunnemann KD (1987) Tobacco-specific A-nitrosamines (TNSA) in green mature and processed tobacco leaves from India. Beitr Tabakforsch 14 29-32... 

Tobacco Specific A -Nitrosamines Occurrence, Carcinogenicity, and Metabolism... 

A series of reviews describing nicotine metabolism has recently appeared [2], Specific topics covered include the biosynthesis and metabolism of nicotine and related alkaloids [3], an overview of mammalian nicotine metabolism [4], the role of cytochrome P450 in nicotine metabolism [5], nicotine metabolism beyond cotinine [6], N-oxidation, A -methylation, and N-conjugation reactions of nicotine [7], extrahepatic metabolism of nicotine and related compounds [8], metabolism of the minor tobacco alkaloids [9], analysis and levels of nicotine and metabolites in body fluids [10], kinetics of nicotine and its metabolites in animals [11], pharmacokinetics of (S)-nicotine and metabolites in humans [12], and sources of inter-individual variation in nicotine pharmacokinetics [13]. Another recent review described variables which affect nicotine metabolism [14]. Several compilations of studies or reviews on the tobacco-specific A-nitrosamines are available [15-18]... 

Jansson, Ch., Paccou, A., and Osterdahl, B.-G., Analysis of tobacco-specific A -nitrosamines in snuff by ethyl acetate extraction and hquid chromatography-tandem mass spectrometry, J. Chromatogr., 1008, 135-143, 2003. 

An automated in-tube solid-phase microextraction HPLC method for NNK and several metabolites have been developed by Mullett et al. ° In-tube SPME is an on-line extraction technique where analytes are extracted and concentrated from the sample directly into a coated capillary by repeated draw-eject steps. A tailor-made polypyrrole-coated capillary was used to evaluate their extraction efficiencies for NNK and several metabolites in cell cultures. This automated extraction and analysis method simplified the determination of the tobacco-specific A-nitrosamines, requiring a total sample analysis time of only 30 min. 

NDMA, A -nitrosodiethylamine, A -nitrosodipropylamine, A -nitrosodibutylamine, A -nitrosopiperidine, A -nitrosopyrrolidine, A -nitrosomorpholine Volatile and tobacco-specific A -nitrosamines, cigarette smoke... 

The identification of various volatile and tobacco-specific A-nitrosamines in tobacco and its smoke and the positive dependence of their levels in both tobacco and smoke on the nitrate level of the tobacco [Morie and Sloan (2635), Tso et al. (3985), Brunnemann et al. (499)]. 

A Brief Chronology of the Research on Tobacco-Specific A/-Nitrosamines... 

FIGURE XV-3 References pertinent to tobacco-specific A -nitrosamines, 1983 to 2004. 

In its 1986 monograph on tobacco smoking, the International Agency for Research on Cancer (lARC) discussed many of the details of A-nitrosamines and tobacco-specific A-nitrosamines in tobacco smoke. Despite the reports prior to 1985 on the identification in tobacco smoke of many nitro components (1755, 1758, 2137, 3086), lARC listed only one nitro compound, 2-nitropropane, as a biologically active smoke component [see Table 19, pp. 86-87 in (1870)]. In its listing of the evaluation of tobacco smoke components for... 

Of the approximately 4800 substances in tobacco smoke (1373), 44 are beheved...to be relevant to tobacco-related diseases (23A06). These include... some volatile carbonyl compounds, tobacco-specific A-nitrosamines, aromatic amines, phenols, volatile alkenes, benzo[a]pyrene and metals. These substances are sometimes called colloquially Hoffmann analytes since similar lists of toxicological substances have been proposed by Dietrich Hoffmann et al. of the American Health Foundation in New York since the mid 1980s. The latest compilation by Hoffmann et al. lists 82 substances (1741,1743, 1744). 

Is the exposure to a given tumorigen less, more, or equal to that from cigarette smoke A detailed account of such alternate exposures requires many pages and tables. Most tumorigens in Table XXVI-1 have many alternate sources. The one obvious exception is the tobacco-specific A-nitrosamines (TSNAs) which, by definition, being tobacco specific, have no alternate. 

Brunnemann et al. (457), Stehhk et al. (3812), Matsushita and Mori (2495), Klus et al. (26A75) unfortunately, the tobacco-specific A-nitrosamine results from a more recent study on ETS by Brunnemann et al. (1992) were not included in the assessment by Guerin et al. (1445) or Holcomb (26A60). 

In Table XXVI-19 is presented a simplified summary of the possible exposures to non-tobacco-specific A-nitrosamines that are known components of tobacco smoke. All ten NNAs... 

Numerous constituents of cigarette smoke have been identified as potential agents of biological damage, including tobacco-specific A-nitrosamines, PAHs, phenolic compounds, and free radicals (746,1727,2999, 3712). 

Adams, J.D., K.D. Brunnemann, and D. Hoffmann Chemical studies on tobacco smoke. LXXV. Rapid method for the analysis of tobacco-specific A-nitrosamines by gas-liquid chromatography with a thermal energy analyzer J. Chromatography 256 (1983) 347-351. 

Pharmacokinetics of tobacco-specific A-nitrosamines in Fischer rats Carcinogenesis 6 (1985) 509-512. 

Adams,J.D.,E.J.LaVoie,M.O Donnell, andD.Hoffmann Pharmacokinetics of tobacco-specific A-nitrosamines in A-Nitroso compounds Occurrence, biological effects and relationship to human cancer edited by I.K. O Neill, R.C. von Borstel, C.T. Miller, J. Long, and H. Bartsch, lARC, Lyon, Prance, lARC Sci. Publ. No. 57 (1984) 779-796. 

Adams, J.D., P. Owens-Tucciarone, and D. Hoffmann Tobacco-specific A-nitrosamines in dry snuff Food Chem. Toxicol. 25 (1987) 245-246. 

Arrendale, R.F., W.J. Chamberlain, O.T. Chortyk, J.L. Baker, and M.G. Stephenson Determination of tobacco-specific A-nitrosamines by capillary gas chromatography/ selected ion monitoring mass spectrometry Anal. Chem. 58 (1986) 565-568. 

Bmnnemann, K.D., J.E. Cox, Y. Liu, and D. Hoffmann Analysis of volatile and tobacco-specific A-nitrosamines in tobacco smoke by conventional method and by supercritical fluid extraction 46th Tobacco Chemists Research Conference, Program Booklet and Abstracts, Vol. 46, Paper No. 22, 1992, pp. 33-34. 

Brunnemann K.D. and D. Hoffmann Analytical stndies on tobacco-specific A-nitrosamines in tobacco and tobacco smoke J. Cancer Res. Chn. Oncol. 116 (Snppl. Pt. 2) (1990) 1087. 

Djordjevic, M.V., B. Prokopczyk, and W. Zatonski Tobacco-specific A-nitrosamines (TSNA) in tobacco and mainstream smoke of the leading Polish cigarettes ... 

Djordjevic, M.V. and S.D. Stellman Acmal dosages of tobacco-specific A-nitrosamines and benzo[a]pyrene 1029. 

Gilhnan, LG. Jr, J.E. Eossett, N. Finkel, and R.D. Bereman Investigations into a rapid method for determining tobacco-specific A-nitrosamines and volatile nitrosamines in sidestream tobacco smoke using LC/ MS/MS with positive ion electrospray 56th Tobacco Science Research Conference, Program Booklet and Abstracts, Vol. 56, Paper No. 36, 2002, p. 41. 

Hoffmann, D., K.D. Brunnemann, and J.D. Adams Tobacco-specific A-nitrosamine (TSNA) Recent progress on occurrence, formation and reduction 8th Internat. 1707. 

Hoffmaim, D., A. Rivenson, S. Amin, and S.S. Hecht Dose-response study of the carcinogenicity of tobacco-specific A-nitrosamines in F344 rats J. Cancer Res. Clin. Oncol. 108 (1984) 81-86. 

Hecht Formation of tobacco-specific A-nitrosamines, their carcinogenicity, and the role of dietary fat in their carcinogenicity 204th Natl. Mtg., Am. Chem. Soc., 1793. 

Tobacco-specific A-nitrosamines Effect of burley alkaloid isolines and nitrogen fertilization management J. 2450a. 

Rivenson, A., S.S. Hecht, and D. Hoffmann Carcinogenicity of tobacco-specific A-nitrosamines... 

Rouse, C. A., J.C. Cunningham, and C.R. Taylor Jr Analysis of tobacco-specific A-nitrosamines in mainstream smoke by supercritical fluid extraction/gas chroma-tography/chemiluminescence detection 53rd Tobacco Science Research Conference, Program Booklet and Abstracts, Vol. 53, Paper No. 50, 1999, pp. 47-A8. 3359. 

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