Tobacco smoke nitrosamine activation

Tobacco Smoke Nitrosamine Activation Oxazaphosphorine Activation. . . ... 

Tobacco smoke and iV-nitrosation are the focus of intense research activity. Workers in the field use the following concepts Tobacco-specific /V-nitrosamines (TSNA) mainstream tobacco smoke (MSTS), smoke inhaled in a puff sidestream tobacco smoke (SSTS), smoke evolved by smoldering cigarettes between puffs nitroso organic compounds (NOC), referring especially to IV-nitrosamines volatile NOC (VNOC) and iV-nitroso amino acids (NAA). 

Pancreatic effect. Cigarette smoke, administered to anesthetized rats alone or in combination with iv ethanol infusion, reduced pancreatic blood flow temporarily and increased leukocyte-endothelium interaction (roller p < 0.001, sticker p < 0.01 vs baseline). Cigarette smoke potentiated the impairment of pancreatic capillary perfusion caused by ethanol, and both the number of rolling leukocytes and myeloperoxidase activity levels were increased compared with ethanol or nicotine administration alone h Tobacco-specific nitrosamines, administered to rats, induced pancreatic acinar cell and ductal cell neoplasms. One of the tumors had a mixed ductal-squamous-islet cell components . 

The volatile A-nitrosamines present in environmental tobacco smoke are one of the classes of toxic air contaminants of particular concern because of their carcinogenicity. The most important four tobacco-specific nitrosamines (TSNA) are A -nitrosonomicotine (NNN), 4-(methylnitros-amino)-l-(3-pyridyl)-l-butanone (NNK), A -nitrosoanabasine (NAB), and A -nitrosoanatabine (NAT). NNN and NNK are known to induce mahgnant tumors in mice, rats, and hamsters. The other nitrosamines do not exhibit significant tumoral activity. 

Crespi, C.L., B.W. Penman, H.V Gelboin, and EJ. Gonzalez (1991). A tobacco smoke-derived nitrosamine, 4-(methylnitrosamino)-1 -(3-pyridyl)-1-butanone, is activated by multiple human cytochrome P450s including the polymorphic human cytochrome P4502D6. Carcinogenesis 12, 1197-1201. 

The only signihcantly tnmorigenic, carcinogenic, or biologically active tobacco and tobacco smoke components discnssed in the 1400-page monograph were the iV-nitrosamines [see pp. 839-844 in Preussmann and Eisenbrand (2990)]. Mnch of the data cited by Dipple et al. were those previously presented by Hoffmann and his colleagnes (514, 1680, 1685). 

It is possible... that little or no nitrosamines are present in cigarette smoke under normal conditions of smoking. Because of the importance of these compounds and the known high incidence of lung cancer, the establishment of their presence in smoke is of importance in the health of man... Even if the nitrosamines are identified and unequivocally established as being present in cigarette smoke at a certain level then it must be investigated whether they contribute to the total toxic activity of tobacco smoke. 

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... 

Radioisotope-labeled nitrosamines have proven valuable in development of analytical methods and for demonstrating efficiency of recovery of nitrosamines from tobacco products and smoke (37-39). The very high specific activity required for low part-per-billion determinations has discouraged most analysts from using this approach. Unless a radiochromatographic detector with adequate sensitivity is available, samples must be counted independently of the final chromatographic determination, and one of the advantages of internal standardization, correction for variation in volume injected, is lost. 

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