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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In summary, evidence from human populations has shown that smokeless tobacco users have risks of cancer several times higher than that of nonsmokers. Smokeless tobacco is very strongly related to cancers of the cheek and gums, locations typically in direct contact with the tobacco. The association is evident in studies in the US and Scandinavia and also in Asia, where the chewing of quids containing tobacco and other ingredients is strongly related to the region's high rates of oral cancer. Reports on health effects date back to the 18th century and the evidence is consistent, with most investigators reporting positive findings. Dose-response relationships--increasing risk with increasing use--are also evident in several studies. Finally, preliminary work on cancers in other anatomic sites suggests that smokeless tobacco may also be related to other upper digestive tract cancers. With the exception of one group of medical scientists who described the relationship as only an "association," expert consensus conferences and committees in both the US and France have agreed that the evidence from clinical, epidemiologic, and carcinogenesis studies supports a causal relationship between the use of smokeless tobacco and oral cancer in humans. These expert groups include the International Agency for Research on Cancer (1984), the National Institutes of Health Consensus Conference on the Health Implications of Smokeless Tobacco Use (1986), and the Surgeon General's Advisory Committee on the Health Consequences of Using Smokeless Tobacco (1986).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Smokeless tobacco and cancer: the epidemiologic evidence. 313 83

Chronic snuff dipping has been associated with oral cancer in man and experimental animals. Here, the effects of a water-extract of snuff on the in-vitro development of human lymphokine-activated killer (LAK) activity were examined. The snuff extract inhibited both LAK cytotoxicity and DNA synthesis in a dose-dependent fashion at concentrations of 0.125 to 2.0 per cent; above 2.0 per cent, cell viability decreased significantly. In contrast, the snuff extract had no effect on natural killer-cell cytotoxicity when incubated with fresh peripheral blood lymphocytes in a standard 4 h assay, or on LAK cytotoxicity when incubated only during the final 4 h effector phase. Lymphocyte protein synthesis was generally unaffected by the addition of this extract. Thus, a water-soluble snuff extract appears to suppress LAK activity by inhibiting DNA synthesis. Altered LAK function in the oral mucosa might permit the development of snuff-associated carcinogenesis.
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PMID:Inhibition of human lymphokine-activated killer activity by smokeless tobacco (snuff) extract. 326 50

Tobacco-specific nitrosamines are a group of carcinogens that are present in tobacco and tobacco smoke. They are formed from nicotine and related tobacco alkaloids. Two of the nicotine-derived nitrosamines, NNK and NNN, are strong carcinogens in laboratory animals. They can induce tumors both locally and systemically. The induction of oral cavity tumors by a mixture of NNK and NNN, and the organospecificity of NNK for the lung are particularly noteworthy. The amounts of NNK and NNN in tobacco and tobacco smoke are high enough that their total estimated doses to long-term snuff-dippers or smokers are similar in magnitude to the total doses required to produce cancer in laboratory animals. These exposures thus represent an unacceptable risk to tobacco consumers, and possibly to non-smokers exposed for years to environmental tobacco smoke. The permission of such high levels of carcinogens in consumer products used by millions of people represents a major legislative failure. Indeed, the levels of tobacco-specific nitrosamines in tobacco are thousands of times higher than the amounts of other nitrosamines in consumer products that are regulated by government authorities. Although the role of tobacco-specific nitrosamines as causative factors in tobacco-related human cancers cannot be assessed with certainty because of the complexity of tobacco and tobacco smoke, several lines of evidence strongly indicate that they have a major role, especially in the causation of oral cancer in snuff-dippers. Epidemiologic studies have demonstrated that snuff-dipping causes oral cancer. NNK and NNN are quantitatively the most prevalent known carcinogens in snuff, and they induce oral tumors when applied to the rat oral cavity. A role for NNK in the induction of lung cancer by tobacco smoke is likely because of its organospecificity for the lung. Tobacco-specific nitrosamines may also be involved in the etiology of tobacco-related cancers of the esophagus, nasal cavity, and pancreas. Because they are derived from nicotine, and therefore should be associated only with tobacco, tobacco smoke and other nicotine-containing products, tobacco-specific nitrosamines as well as their metabolites and macromolecular adducts should be ideal markers for assessing human exposure to, and metabolic activation of, tobacco smoke carcinogens. Ongoing research has demonstrated the formation of globin and DNA adducts of NNK and NNN in experimental animals. Sensitive methods for the detection and quantitation of these adducts in humans would provide an approach to assessing individual risk for tobacco-related cancers.(ABSTRACT TRUNCATED AT 400 WORDS)
Carcinogenesis 1988 Jun
PMID:Tobacco-specific nitrosamines, an important group of carcinogens in tobacco and tobacco smoke. 328 30

It is considered that the great majority of head and neck squamous cell cancers are self-inflicted cancers. The main high-risk factor for squamous cell cancers of the oro-airway region is heavy smoking. Well-known habits of smoking include reverse smoking and betel nut chewing in South Asia. Tobacco smoking has distinct carcinogenecity as both an initiator and promoter. Also the risks associated with smoking and alcohol consumption are synergistic. There are many adjuvant carcinogens which act as promoting factors and which are also causes of cancer in the head and neck area. Distinct promotion factors are poor dental hygiene for mouth cancer, vocal abuse in laryngeal cancer, Plummer-Vinson's syndrome in post-cricoid cancer and chronic sinusitis in maxillary cancer. High-risk factors for carcinogenesis in the larynx are smoking (Brinkman index, over 600), heavy drinking, being over 50 years of age in males and anyone with a husky voice and abnormal sensation in the throat. In the piriform sinus, main risk factors of carcinogenesis are heavy smoking and drinking in males and in the post-cricoid area, those most at risk are female patients with Plummer-Vinson's syndrome. The prevention of head and neck cancers involves discouragement from smoking, and earlier detection of these cancers is very important. If early detection can be achieved, the highest cure rate among human cancers will be achieved.
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PMID:[High-risk factors in the development of head and neck cancers]. 363 66

Yeasts were isolated from 12 cases of oral precancerous lesions (leukoplakia and erythroleukoplakia) by sampling the lesion as well as normal mucosa of each patient, yielding 21 strains of Candida albicans belonging to 15 biotypes, two strains of C. tropicalis, one strain of C. parapsilosis and two strains of Torulopsis glabrata. Biopsies were obtained from the lesions for histologic examination. The catalytic potential of the yeast strains to form N-nitrosobenzylmethylamine (NBMA) from the precursors N-benzylmethylamine and nitrite was assessed at pH 6.8. The NBMA produced was identified and quantitated by h.p.l.c. and confirmed by g.c.-m.s. Nitrosation rates were calculated as total nitrosamine subtracted the chemically produced nitrosamine, and related to number of yeast cells. The yeast strains differed in nitrosation potential (P less than 0.001), ranking from 0 to 1.2 micrograms NBMA/10(6) cells. Candida albicans strains, belonging to the biotypes 051, 147, 151, 153, 157 and 353, which constitute more rarely occurring biotypes, exhibited the highest nitrosation potential. Candida tropicalis, C. parapsilosis and T. glabrata were ranked lower. Strains with high nitrosation potential were generally isolated from lesions with more advanced precancerous changes. The yeast cells were present in the superficial part of the epithelium of the lesions as branching mycelium, and in some cases extending from the mucosal surface to the deeper epithelial cell layers. This might represent a fungal transportation system which could channel precursors in the saliva at the mucosal surface to the deeper part of the epithelium where the produced nitrosamine could be deposited. Thus, further evidence is provided supporting the hypothesis that certain strains of C. albicans and of other yeasts play a causal role in the development of oral cancer, by means of endogenous nitrosamine production.
Carcinogenesis 1987 Oct
PMID:Possible mycological etiology of oral mucosal cancer: catalytic potential of infecting Candida albicans and other yeasts in production of N-nitrosobenzylmethylamine. 365 90

Exfoliated mucosal cells were collected from the oral cavity of three groups at high risk for oral cancer: Indian betel nut chewers, Filipino inverted smokers (burning end of cigar in mouth) and Indian Khaini tobacco chewers. DNA was extracted from these samples, as well as from samples of exfoliated cells of Canadian non-smoking controls. DNA was analyzed for the presence of aromatic DNA adducts using 32P-postlabelling analysis. Five chromatographically distinct adducts were found in samples from both the high risk groups and the nonsmoking controls. Individual adducts were detectable in approximately 30-95% of samples, depending on the adduct and population group. Estimated levels of specific adducts ranged from non-detectable (prevalence relative to normal nucleotides less than 1 X 10(-9)) to occasionally greater than 1 X 10(-7). No adducts were found in high risk groups which did not also appear in control subjects.
Carcinogenesis 1986 Jul
PMID:32P-postlabelling analysis of aromatic DNA adducts in human oral mucosal cells. 371 6

The results of a survey of a population with a high incidence of oral cancer are presented in this paper. A remarkably high proportion (41%) of the men surveyed used nass, which is a mixture of tobacco, lime, ash, and cotton oil. The prevalence of oral leukoplakia, lesions thought to be a precursor of oral cancer, was high in persons who used nass (12%) and who smoked cigarettes (15%), and highest among those men who both used nass and smoked (21%). It has been shown that nass use increases the frequency of micronucleated cells in the exfoliated sublingual cells. The clastogenic and genotoxic effect of nass revealed in the study could be attributed to the presence of tobacco-specific N-nitroso compounds. However, the results of chemical analysis, which has shown that nass contains relatively low levels of these compounds, suggest that the relatively strong genotoxic activity of nass could primarily be associated with other chemicals, possibly oxidized phenolics. Despite the uncertainty as to which of the chemicals contained in nass are involved in the etiology of oral cancer and what exactly are the mechanisms of nass-induced carcinogenesis, the results of this study suggest that in populations where nass is widely used, oral leukoplakia and, most probably, oral cancer are conditions that could be prevented by the elimination of nass use and cigarette smoking.
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PMID:The effect of nass use and smoking on the risk of oral leukoplakia. 377 5

Most reported studies of experimental oral cancer have been carried out in the hamster. This animal is not available in certain countries and there is controversy regarding its suitability as a model for experimental oral carcinogenesis. An attempt was made to reproduce an experimental oral cancer model in rats, using a protocol based on that described by Lekholm and Wallenius (1976). The carcinogen 4 nitroquinoline 1-oxide was applied to the palates of rats for periods of up to 24 weeks. Macroscopic and microscopic examination of carcinogen-treated palatal mucosa was carried out during the experimental period. Verrucous carcinoma-like lesions of the mid-palate and squamous carcinomas of the gingival mucosa were produced, beginning at 16 and 20 weeks respectively. A variety of other macroscopic and microscopic mucosal changes were also observed during the experimental period. The findings are discussed in relation to the work of others.
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PMID:4 Nitroquinoline 1-oxide-induced carcinogenesis in the rat palate. 641 58

I present evidence in support of a chemopreventive role for the so-called antioxidant nutrients, beta-carotene and vitamin E, against oral cavity cancer. This evidence is from laboratory studies, animal model systems, epidemiologic surveys, intervention trials involving reversal of premalignant changes, and prevention of malignancies in particularly high-risk subjects. Because agents proposed for disease prevention are meant to be used widely without close medical supervision, almost any toxicity is unacceptable. beta-Carotene and vitamin E fulfill this criterion for a suitable chemopreventive agent. In several epidemiologic studies, low intakes of vitamin E, carotenoids, or both have been associated with a higher cancer risk. Smoking, a major risk factor, results in lower beta-carotene concentrations in plasma and oral mucosal cells. In several laboratory and animal model systems, beta-carotene and other antioxidant nutrients are inhibitors of oral cavity carcinogenesis. beta-Carotene and vitamin E can produce clinical regression of oral leukoplakia, a premalignant lesion for oral cancer. The design and limitations of such studies in oral leukoplakia are discussed. Cancer incidence reduction trials in high-risk groups have targeted prevention of second malignancies in patients cured of a primary oral cancer. These trials are in progress. The data thus far are supportive of a significant preventive role for these nutrients in oral cancer.
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PMID:Antioxidants in oral cancer prevention. 749 39

We have identified, isolated, and partially characterized doc-1, a novel cDNA sequence whose activity is consistent with a suppressor of hamster oral carcinogenesis. Doc-1 is an evolutionarily conserved gene exhibiting loss of heterozygosity and marked reduction in expression in malignant hamster oral keratinocytes. The full-length doc-1 cDNA encodes an 87 amino acid product that shows a significant homology to one of the seven novel genes induced in mouse fibroblasts by TNF-alpha. Transfection of the full-length doc-1 cDNA into malignant hamster oral keratinocytes alters the behavior of the recipients in terms of morphology, growth rate, and anchorage-independent growth, suggesting reversion of transformation phenotypes. We propose that doc-1 is a novel tumor suppressor gene in oral cancer development.
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PMID:Deleted in oral cancer-1 (doc-1), a novel oral tumor suppressor gene. 755 27


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