Carcinogenesis
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The origin of tobacco-specific nitrosamines (TSNA) in mainstream smoke and the possible contribution of synthesis during the smoking procedure was investigated. Addition of the nitrosamine precursors nitrate and nicotine to the tobacco prior to smoking did not change the mainstream smoke concentrations of N'-nitrosonornicotine (NNN) and 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone (NNK), whereas the mainstream smoke concentration of N'-nitrosoanabasine (NAB) and N'-nitrosoanatabine (NAT) increased after spiking the cigarettes with nitrate. Data for TSNA in tobacco and in mainstream smoke and for nitrate in tobacco of commercial cigarettes of the West German market, taken from previous investigations, were used to calculate the mainstream smoke/tobacco ratios for NNN and NNK. ⋯ Furthermore it is shown that the mainstream smoke/tobacco ratios for NNN and NNK are constant over the whole length of the cigarettes except for NNK in dark tobacco type cigarettes. The results of this investigation indicate that pyrosynthesis of NNN does not occur and that it is very unlikely for NNK at least for lower nitrate levels. Thus with few exceptions the TSNA burden of smokers is predominantly influenced by the amount of preformed NNN and NNK in tobacco.
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Comparative Study
Preformed tobacco-specific nitrosamines in tobacco--role of nitrate and influence of tobacco type.
Fifty-five types of commercial cigarettes on the open market in the FRG and several samples of pure tobacco types were analyzed for preformed tobacco-specific nitrosamines (TSNA) and nitrate in the tobacco. For the cigarette tobaccos the observed range for N'-nitrosonornicotine (NNN) was 50-5316 ng/cigarette and for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) from not detected (less than 50 ng/cigarette) to 1120 ng/cigarette. Nitrate levels ranged from 0.6 to 14.4 mg/cigarette. ⋯ Virginia tobaccos which show a low nitrate content are low in NNN but rather high NNK concentrations were found. The results from these pure tobacco types demonstrate that the nitrate content of the tobacco has a great influence on the TSNA level. However, Virginia tobaccos show higher NNK concentrations than expected according to their low nitrate content.
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Administration of ethionine resulted in a dose- and time-dependent enhancement of the activities of peroxisomal beta-oxidation, carnitine palmitoyltransferase and omega-oxidation, especially the 12-hydroxylation of lauric acid. The mitochondrial and, especially, the microsomal palmitoyl-CoA hydrolase activities were increased, whereas the peroxisomal and cytosolic activities were decreased. Ethionine administration decreased the catalase and urate oxidase activities in both a dose- and time-related manner. ⋯ The amount of GSH and the level of peroxisomal beta-oxidation were significantly increased in liver at an ethionine dose of 100 mg/day/kg body weight. These responses in liver were evident within 2 days of ethionine exposure and then leveled off whereas a significant increase in GSH and peroxisomal beta-oxidation in kidney was observed within 12 days. Whether the acute H2O2-generating peroxisomal oxidation of long-chain fatty acids in the liver may also make this organ susceptible to the long-term effects of low-dose ethionine and be an important step in the chain of events which eventually results in tumour development should be considered.
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Fifty-five types of commercial cigarettes on the West German market were analyzed for tobacco-specific nitrosamines (TSNA) in mainstream smoke. The cigarettes included filter and nonfilter cigarettes with very high, high, medium, low and ultra-low tar and nicotine yields. The observed range for N'-nitrosonornicotine was from 5 to 625 ng/cigarette and for 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone from not detected (less than 4 ng/cigarette) to 432 ng/cigarette. ⋯ The results demonstrated that there is no correlation between TSNA and tar deliveries in mainstrain smoke. The TSNA deliveries in mainstream smoke depended on the actual tobacco composition. According to these results the tar delivery, although crucial, is not a sufficient index for the biological activity and the carcinogenic potential of cigarette smoke.
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The immunoreactivity of normal human and Bloom's syndrome uracil DNA glycosylase was examined using a series of three anti-human placental uracil DNA glycosylase monoclonal antibodies. Immunoreactivity was determined by three separate and independent criteria: enzyme-linked immunosorbent assay (ELISA), enzyme inhibition studies and immunoblot analysis. As defined by each criteria, normal human uracil DNA glycosylase was immunoreactive with each antibody (37.04.12, 40.10.09 and 42.08.07). ⋯ However, immunoreactivity of the denatured Bloom's syndrome enzyme with 40.10.09 antibody was observed by immunoblot analysis. These results suggest that Bloom's syndrome uracil DNA glycosylase is characterized by a structural alteration in the native glycosylase protein secondary to the primary antigenic site recognized by the 40.10.09 antibody. This altered antigenicity may provide an immunological marker for the identification of this human genetic syndrome.