ISSN:1040-8444    

DOI:10.3109/10408449609017925

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractTobacco-specificN-nitrosamines (TSNA) are the most abundant, strong carcinogens in tobacco smoke. Seven TSNA have been identified in tobacco products:Nω-nitrosonornicotine (NNN),Nω-nitrosoanabasine (NAB),N-nitrosoanatabine (NAT), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), 4-(methylnitrosamino)-4-(3-pyridyl)-1-butanol (iso-NNAL), and 4-(methylnitrosamino)-4-3-pyridyl)butyric acid (iso-NNAC). The syntheses of these compounds are reviewed. The syntheses of14C- and3H-labeled NNK as well as metabolites of NNK and NNN are also discussed.Comparative assays for lung tumorigenesis in femaleNmice were carried out for six of the TSNA and for two related compounds,N-nitrosodimethylamine (NDMA) andN-nitrosopyrrolidine (NPYR). They yielded the following ranking of potency: NDMA>NNK>NNAL>NPYR>NNN>NAB.Iso-NNAL andiso-NNAC were inactive. These results are also compared with previous assays of TSNA carcinogenicity in rats and hamsters.

ISSN:1040-8444    

DOI:10.3109/10408449609017927

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractOne-third of all cancers worldwide can be attributed to various tobacco habits. Both in tobacco smoke and smokeless tobacco, carcinogenicN-nitroso compounds (NOC) are implicated as DNA-damaging agents in cancers of the aerodigestive tract and the pancreas. The exposure from nitrosamines in certain types of tobacco use such as“toombak”in Sudan could be as high as a few milligrams per day. Using theN-nitrosoproline test, it has been shown that smoking contributes to endogenous nitrosation and likely increases NOC formationin vivo. Smokeless tobacco, most widely used in the form of chewing of betel quid (BQ) with tobacco, was shown to particularly enhance endogenous nitrosation in the oral cavity, a site where chewing habits are causally associated with cancer. Poor oral hygiene was found to contribute to the formation of nitrosamines in the oral cavity. The evidence so far accumulated demonstrates that tobacco habits increase endogenous NOC formation, thus adding to the burden of exposure by preformed carcinogenic NOC in tobacco products. In snuff dippers, the unexpected higher level of HPB released from hemoglobin, an exposure marker for carcinogenic tobacco-specific nitrosamines, has been attributed to the endogenous formation of these carcinogens. Recent studies have demonstrated that besides carcinogenic tobacco-specific nitrosamines, reactive oxygen species derived from BQ ingredients could also play a role in the etiology of oral cancer in chewers. Although the use of chemopreventive agents may block nitrosation reactionsin vivoin tobacco users, cessation of tobacco habits is the only safe way for an efficient reduction of cancer risk, in view of the high exposure to other (preformed) tobacco-related carcinogens.

ISSN:1040-8444    

DOI:10.3109/10408449609017928

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractThis article reviews recent advances in the biochemistry and molecular biology of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a tobacco-specific pulmonary carcinogen believed to be involved in the induction of lung cancer in smokers. Several aspects of NNK bioactivation are addressed, including identification of its metabolites in laboratory animals and humans, cytochrome P450 enzyme involvement in its metabolic activation, DNA and protein adduct formation, biological significance of the major DNA adducts formed, and mutations in oncogenes from tumors induced by NNK. Collectively, the presently available data provide a reasonably clear picture of NNK bioactivation in rodents, although there are still important gaps in our mechanistic understanding of NNK-induced tumorigenesis. The studies in rodents and primates have facilitated development of methods to assess NNK bioactivation in humans, which will be applicable to studies of lung cancer susceptibility and prevention.

ISSN:1040-8444    

DOI:10.3109/10408449609017929

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractGlobally, oral cancer is one of the ten common cancers. In some parts of the world, including the Indian subcontinent, oral cancer is a major cancer problem. Tobacco use is the most important risk factor for oral cancer. The most common form of tobacco use, cigarette smoking, demonstrates a very high relative risk—in a recent cohort study (CPS II), even higher than lung cancer. In areas where tobacco is used in a smokeless form, oral cancer incidence is generally high. In the West, especially in the U.S. and Scandinavia, smokeless tobacco use consists of oral use of snuff. In Central, South, and Southeast Asia smokeless tobacco use encompassesnass, naswar, khaini, mawa, mishri, gudakhu, and betel quid. In India tobacco is smoked in many ways; the most common isbidi, others beingchutta, including reverse smoking,hooka, and clay pipe. A voluminous body of research data implicating most of these forms of tobacco use emanates from the Indian subcontinent. These studies encompass case and case-series reports, and case-control, cohort, and intervention studies. Collectively, the evidence fulfills the epidemiological criteria of causality: strength, consistency, temporality, and coherence. The biological plausibility is provided by the identification of several carcinogens in tobacco, the most abundant and strongest being tobacco-specificN-nitrosamines such asN-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These are formed byN-nitrosation of nicotine, the major alkaloid responsible for addiction to tobacco. The etiological relationship between tobacco use and oral cancer has provided us with a comprehensive model for understanding carcinogenesis.

ISSN:1040-8444    

DOI:10.3109/10408449609017930

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractIn the U.S., there has been a steeper rise of the incidence of lung adenocarcinoma than of squamous cell carcinoma of the lung among cigarette smokers. Since 1950, the percentage of all cigarettes sold that had filter tips increased from 0.56 to 92% in 1980 and to 97% in 1990. The tobacco of the filter cigarettes is richer in nitrate than that of the nonfilter cigarettes manufactured in past decades. Because the smoker of cigarettes with lower nicotine yield tends to smoke more intensely and to inhale the smoke more deeply than the smoker of plain cigarettes, the peripheral lung is exposed to higher amounts of nitrogen oxides, nitrosated compounds, and lung-specific smoke carcinogens. It is our working hypothesis that more intense smoking, deeper inhalation of the smoke, and higher smoke delivery of the organ-specific lung carcinogen NNK to the peripheral lung are major contributors to the increased risk of cigarette smokers for lung adenocarcinoma. Bioassay data and biochemical studies in support of this concept are discussed.

ISSN:1040-8444    

DOI:10.3109/10408449609017931

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

摘要:

AbstractComplex mixtures that are produced from the combustion of organic materials have been associated with increased cancer mortality. These mixtures contain homocyclic and heterocyclic polycyclic aromatic hydrocarbons (PAHs), many of which are known carcinogens. In particular,N-heterocyclic aromatic compounds (NHA) are present in these mixtures. Studies to determine the metabolic activation of these compounds have been undertaken. The purpose of this review is to compare and contrast the metabolic activation and biological effects of two NHA, 7H-dibenzo[c,g]carbazole (DBC) and dibenz[a,j]acridine (DBA), in order to better assess the contribution of NHA to the carcinogenic potency of complex mixtures and to develop biomarkers of the carcinogenic process. DBC has both local and systemic effects in the mouse; it is a potent skin and liver carcinogen following topical application and a lung carcinogen following i.p. application. On the other hand, DBA is a moderate mouse skin carcinogen following topical application and a lung carcinogen following subcutaneous injection. The biological differences for DBC and DBA are reflected in target organ-specific proximate and mutagenic metabolites and DNA adduct patterns.

ISSN:1040-8444    

DOI:10.3109/10408449609017932

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor

ISSN:1040-8444    

DOI:10.3109/10408449609017933

出版商:Taylor&Francis    

年代:1996

数据来源: Taylor