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

The ultimate proof that a putative chemopreventive agent does prevent cancer is a demonstration of reduced cancer incidence in a targeted population. However, because of practical and logistical considerations, such trials are virtually impossible to conduct for the majority of cancers. Therefore, a conclusion regarding the efficacy of chemopreventive activity is based on consideration of a variety of indirect lines of evidence, including laboratory studies, animal model systems, epidemiologic surveys, intervention trials involving reversal of premalignant changes, and the prevention of malignancies in particularly high risk subjects. Furthermore, the only agents worth testing are those with limited, or preferably, no toxicity, since the final use will be prevention in a generally healthy population. Beta-carotene and vitamin E both fulfill all the criteria for suitable chemopreventive agents; several lines of evidence point toward preventive roles for them in oral cancer. In numerous epidemiologic studies, low intake of beta-carotene has been associated with higher cancer risk. Both intake and supplemental use of vitamin E have been associated with a lowered risk of cancer. Smokers, whose habit is a major risk factor, have lower beta-carotene levels in oral mucosal cells when compared with non-smokers. In several laboratory and animal model systems, including the very relevant hamster cheek pouch model, these agents strongly inhibit oral cavity carcinogenesis. Beta-carotene and vitamin E produce regression of oral leukoplakia, a premalignant lesion for oral cancer. This has now been shown in seven clinical trials: five with beta-carotene alone, one with vitamin E, and one with a combination of both.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beta-carotene and vitamin E in oral cancer prevention. 841 3

The inhibitory effect of dietary supplementation with flavonol quercetin on 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch carcinogenesis was investigated. Dietary quercetin inhibited the incidence of both papillomas and tumors induced by DMBA. The fluorescence spectra of papillomas and tumors showed different prominent maxima and a characteristic peak around 620-630 nm, which could be attributed to the accumulation of porphyrin compounds. Further, the fluorescence intensities at 630 nm (FI630nm) were elevated, whereas the ratio FI530nm/FI630nm was decreased in DMBA-induced lesions. Quercetin treatment significantly decreased FI630nm and increased the ratio FI520nm/FI630nm when compared with DMBA-induced lesions. It is therefore evident that quercetin has an inhibitory effect on DMBA-induced carcinogenesis and further studies will throw more light on its use as a chemopreventive agent against oral cancer.
Carcinogenesis 1996 Apr
PMID:Inhibitory effect of dietary flavonol quercetin on 7,12-dimethylbenz[a]anthracene-induced hamster buccal pouch carcinogenesis. 862 4

The effect of a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate (ACA), on 4-nitroquinoline 1-oxide (4-NQO)-induced oral carcinogenesis was investigated in male F344 rats. All rats except those in the ACA-alone and untreated groups were given 4-NQO (20 ppm) In the drinking water for 8 weeks to induce oral cancer. Starting 1 week before the 4-NQO exposure, animals were fed diet containing 100 ppm or 500 ppm ACA for 10 weeks, followed by the basal diet without ACA for 22 weeks. Other groups were fed the diet containing ACA at 100 ppm or 500 ppm for 22 weeks, starting 1 week after the cessation of 4-NQO exposure. The remaining groups consisted of rats given 500 ppm ACA alone or untreated rats. At the termination of the experiment (32 weeks), the incidences of tongue neoplasms and preneoplastic lesions, polyamine levels in the tongue tissue, and cell proliferation activity estimated in terms of 5-bromodeoxyuridine (BrdU)-labeling index and by morphometric analysis of silver-stained nucleolar organizer regions' protein (AgNORs) were compared among the groups. Feeding of ACA at the two doses during initiation or postinitiation significantly decreased the development of tongue carcinoma (93-100% reduction, P < 0.001) and preneoplasia (43-50% reduction for hyperplasia and 34-48% reduction for dysplasia, P < 0.05). There were no such lesions in rats fed ACA alone or those in the untreated control group. The number of AgNORs per cell nucleus was significantly decreased by feeding of ACA at a high dose (500 ppm) (29% inhibition, P < 0.05). The BrdU-labeling index was also reduced by dietary administration of ACA (23-32% inhibition, P < 0.01). In addition, ACA feeding reduced tongue polyamine levels (35-40% inhibition, P < 0.05). These results indicate that ACA inhibited rat oral carcinogenesis, and such inhibition might be related to suppression of cell proliferation in the oral mucosa by the xanthine oxidase inhibitor.
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PMID:Chemopreventive effect of a xanthine oxidase inhibitor, 1'-acetoxychavicol acetate, on rat oral carcinogenesis. 864 65

Globally, 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 encompasses nass, naswar, khaini, mawa, mishri, gudakhu, and betel quid. In India tobacco is smoked in many ways; the most common is bidi, others being chutta, 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-specific N-nitrosamines such as N-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). These are formed by N-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.
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PMID:Epidemiology of cancer by tobacco products and the significance of TSNA. 868 60

With the ultimate goal of characterizing the molecular pathogenesis of oral cancer, the most predominant malignancy in India, immunocytochemical evaluation of p53 and bcl-2 proteins was carried out in hypeplastic oral mucosa, dysplastic oral mucosa and invasive oral cancer. All subjects gave a similar and almost uniform history of prolonged use of betal quid and tobacco. Expression of p53 was insignificant while bcl-2 was absent in hyperplastic leukoplakia lesions. Both proteins were however expressed in leukoplakia with apparent dysplasia. Almost all invasive cancer lesions showed high levels of both p53 and bcl-2. Good correlation was therefore evident between expression of these two proteins and increasing histologic abnormality. Moreover relative risk evaluation revealed that lesions expressing p53 and bcl-2 had a high probability of having a histology of dysplasia or worse. Since it has been previously shown that wild type p53 regulates the expression of bcl-2, it may be presumed that the protein detected in the dysplastic and malignant oral tissue is of the mutant type. It is also known that p53 is a positive regulator of programmed cell death or apoptosis while bcl-2 is an anti-apoptotic protein. This suggests the possibility that alterations in p53 followed by over-expression of bcl-2 occur early in oral carcinogenesis resulting in defective apoptosis and subsequent tumor progression.
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PMID:Expression of programmed cell death regulatory p53 and bcl-2 proteins in oral lesions. 869 36

Carcinogenesis by 4-nitroquinoline-1-oxide (NQO) in the oral mucosa is a reliable method of obtaining oral mucosal squamous cell carcinoma (OMSCC) and allows examination of various stages of oral cancer development. In vivo and in vitro studies have indicated that L-ascorbic acid (AA) may have a role in cancer prevention. The Wistar "scurvy-prone" osteogenic disorder Shionogi (ODS) rat of the od/od substrain is unable to synthesize AA and requires supplementation for its survival. This study examined the effects of NQO on the oral mucosa of ODS and outbred Wistar rats. NQO (0.5%) was applied topically to the palatal mucosa of 72 male ODS and 36 outbred Wistar rats three times weekly for 4, 8, 12, 16, 20, and 24 wks. The ODS rats were divided so that 36 rats were given 2.5 g/l AA in the drinking water and 36 rats were given 0.33 g/l AA. Vehicle-treated and untreated control animals were included. The rats were killed two weeks after the final NQO application, and the tissues were examined. Epithelial dysplasia was assessed using a modified Smith and Pindborg (1969) index. The ordered categorical scores were analyzed appropriately. Plasma AA levels were checked in ODS and outbred rats at the start and end of the experiment. The results indicated that the oral mucosa of the ODS and outbred rats were susceptible to NQO but that the rate of dysplasia and OMSCC development differed between them, with more rapid changes being found in the ODS rats (p < or = 0.05). No significant difference was found in the dysplasia scores and in the rate of OMSCC development between ODS rats given 2.5 g/l of AA and ODS rats given 0.33 g/l of AA (p > 0.05). No epithelial changes were observed in the palatal mucosa of vehicle-treated and untreated controls. The plasma AA level mean (+/- SEM) was 56 +/- 6 microM for the outbred rats, 8 +/- 1 microM for the ODS rats given 0.33 g/l AA supplementation, and 29 +/- 2 microM for the ODS rats given 2.5 g/l AA. It was concluded that the chronic AA-deficient state in ODS rats played an insignificant role in oral carcinogenesis and that other factors, for example, genetic differences in susceptibility to NQO, contributed to the present findings.
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PMID:Induction by 4-nitroquinoline-1-oxide of oral epithelial dysplasia and neoplasia in scurvy-prone osteogenic disorder Shionogi (ODS) rats. 884 24

India has one of the world's highest incidences of oral cancer. It is believed that the widespread habit of betel quid chewing is an important risk factor as it exposes the oral mucosa to known carcinogens. It also induces physical abrasions, which may create mitogenic environments during wound healing as gateways for infections. A recent study from our laboratories identified human papillomavirus (HPV) DNA, mostly of the high-risk types HPV-16 and HPV-18, in 67 of 91 oral cancer lesions from a cohort of Indian patients consisting mostly of betel quid users. This suggested a viral etiology of some lesions but tumorigenesis in the absence of viruses in other lesions. Here, we examined whether the p53 gene, whose function is abrogated by the product of the HPV gene E6, would be mutated in those oral cancers that were free of HPV DNA, and we found point mutations at known hot spots for mutational alteration of p53 in 4 of 23 lesions. We also considered the possibility that p21, a target of regulation by the p53 protein, may be mutationally altered in tumors with a functional p53 gene. While we did not identify mutations in the p21 gene, 6 of 11 lesions contained a polymorphism that may be associated with cancer. Interestingly, 3 of 23 lesions had mutations in the p16 gene, a third regulator of the cell cycle which is frequently mutated in melanoma but rarely in other cancers, with 1 lesion even having a mutation in the p53 as well as in the p16 gene. Our data point to p53 and p16 as gene targets of oral carcinogenesis, with chemicals in the betel quid possibly functioning in these tumors as carcinogens.
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PMID:Mutations and polymorphisms in the p53, p21 and p16 genes in oral carcinomas of Indian betel quid chewers. 894 9

During normal cellular metabolism, free oxygen radicals are constantly generated. These are extremely toxic. However, they are rapidly eliminated by a series of metabolic steps, which involve certain enzymes such as superoxide dismutase, catalase and glutathione peroxidase (a selenium dependent enzyme). The toxic effect of free oxygen radicals has been suggested to have carcinogenic properties, and this hypothesis may be the link between low selenium levels and increased cancer morbidity. From this point of view a correct selenium concentration in the plasma may represent a form of chemioprevention. In fact, the concept of chemioprevention of carcinogenesis with inhibitory chemical compounds is particularly apropous to head and neck squamous cell cancer control, because the incidence of metachronous second primary tumours in surviving patients with oral cancer is very high.
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PMID:[Selenium and oral cancer. Review of the literature]. 898 28

The modifying effects of the two flavonoids diosmin and hesperidin given during the initiation and postinitiation phases of oral carcinogenesis initiated with 4-nitroquinoline 1-oxide (4-NQO) were investigated in male F344 rats. The compounds were tested alone and in combination. At 6 weeks of age, animals were divided into experimental and control groups and fed diets containing 1000 ppm diosmin and 1000 ppm hesperidin and a diet containing both compounds (900 ppm diosmin and 100 ppm hesperidin). At 7 weeks of age, all animals except those treated with each test chemical alone and control groups were given 4-NQO (20 ppm) in the drinking water for 8 weeks to induce oral cancer. Starting 7 days before the 4-NQO exposure, groups of animals were fed the diets containing test chemicals for 10 weeks and then switched to the basal diet. Starting 1 week after the cessation of 4-NQO exposure, the groups given 4-NQO and a basal diet were switched to the diets containing diosmin, hesperidin, or diosmin combined with hesperidin and maintained on these diets for 22 weeks. The other groups consisted of rats given diosmin (1000 ppm), hesperidin (1000 ppm), and the combination regimen of these two compounds (900 ppm diosmin with 100 ppm hesperidin) alone, and untreated rats. All animals were necropsied at the termination of the study (week 32). The incidences of tongue lesions (neoplasms and preneoplasms), polyamine levels in the tongue tissue, and cell proliferation activity estimated by a 5-bromodeoxyuridine-labeling index and by morphometric analysis of silver-stained nucleolar organizer regions protein were compared among the groups. Feeding of both compounds singly or in combination during the initiation phase caused a significant reduction in the frequency of tongue carcinoma [diosmin, 68% reduction (P < 0.01); hesperidin, 75% reduction (P < 0.005); and the combination regimen, 69% (P < 0.05)]. When fed the test compounds singly or the combination regimen after 4-NQO exposure, the frequency of tongue cancer was also decreased [diosmin, 77% reduction (P < 0.005); hesperidin, 62% reduction (P < 0.05); and the combination regimen, 77% (P < 0.005)]. The incidences of oral preneoplasia (hyperplasia and dysplasia) in these groups were also decreased when compared with carcinogen controls (P < 0.05-P < 0.001). There were no pathological alterations in rats treated with test compounds or the combined regimen alone or those in an untreated control group. Dietary administration of these compounds significantly decreased the expression of cell proliferation biomarkers (5-bromodeoxyuridine-labeling index and silver-stained nucleolar organizer regions protein number) of the nonlesional tongue squamous epithelium (P < 0.05). Also, polyamine concentrations in the oral mucosa were lowered in rats given the carcinogen and test compounds, alone and in combination, compared with those of rats given 4-NQO alone (P < 0.05). These findings suggest that supplementation with the flavonoids diosmin and hesperidin, individually and in combination, is effective in inhibiting the development of oral neoplasms induced by 4-NQO, and such inhibition might be related to suppression of increased cell proliferation caused by 4-NQO in the oral mucosa.
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PMID:Chemoprevention of 4-nitroquinoline 1-oxide-induced oral carcinogenesis in rats by flavonoids diosmin and hesperidin, each alone and in combination. 900 May 63

We have isolated a human cDNA encoding a 115-amino-acid polypeptide that revealed 97% identity to a candidate tumor suppressor gene for oral cancer in Mesocricetus auratus (deleted in oral cancer-1; doc-1). It also showed a high degree of homology to a gene induced by TNF-alpha in Mus musculus. To investigate its possible role in esophageal carcinogenesis, we examined genetic alterations and expression levels of the gene in 13 esophageal carcinoma cell lines and 10 primary esophageal carcinomas. No mutation nor reduction of expression was observed in any of the 23 cancer materials examined. These results imply that the human doc-1 homologue is unlikely to play a significant role in esophageal carcinogenesis, although its role in the TNF-alpha signaling pathway remains unclear. We mapped DOC1 to chromosome band 12q24.31 by fluorescence in situ hybridization.
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PMID:Isolation, mapping and mutation analysis of a human cDNA homologous to the doc-1 gene of the Chinese hamster, a candidate tumor suppressor for oral cancer. 933 72


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