Micronuclei and carcinogen DNA adducts as intermediate end points in nutrient intervention trial of precancerous lesions in the oral cavity

Prasad, Mahendra; Mukundan, M.A.; Krishnaswamy, Kamala

doi:10.1016/0964-1955(95)00013-8

Cited by 44 publications

(15 citation statements)

References 16 publications

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“…Em geral, a ação carcinogêni-ca do álcool ocorre em níveis de exposição superiores a 45 ml de etanol por dia. Em nossa amostra constituída por indivíduos alcoólatras com ausên-cia de neoplasia maligna oral, constatou-se que o menor consumo de etanol foi de 34,7 ml/dia e o maior de 1.825 ml/dia, com exposição média de A obtenção dos dados referentes ao consumo de álcool e de fumo mediante registro em questionário tem sido largamente utilizada em diversos estudos 7,14,17,18 . Algumas dificuldades têm sido relatadas nos estudos referentes ao tipo de bebida e risco de câncer bucal.…”

Section: Discussionunclassified

“…Como as interações do DNA com substâncias químicas são reconhecidamente o primeiro passo na iniciação do câncer, maior ênfase deve ser dada aos métodos que detectam a atividade genotóxica em humanos 9,17 . Os biomarcadores podem ser utilizados na prevenção individual de tumores e, principalmente, na detecção de pacientes de alto risco 17 . Os micronúcleos contêm material genético que foi perdido do genoma durante a mitose, como resultado de eventos clastogênicos ou aneugênicos e ocorrem antes de qualquer mudança histopatológica pré-neoplásica tornar-se evidente 3,25 .…”

Section: Discussionunclassified

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Efeito genotóxico do etanol em células da mucosa bucal

Reis

Sadigursky

Andrade

et al. 2002

Pesqui. Odontol. Bras.

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RESUMO:O etanol é um dos agentes químicos relacionados ao desenvolvimento de neoplasias malignas bucais. Os micronúcleos são porções de cromatina que permanecem próximas ao núcleo, resultantes de mitoses aberrantes após a ação de agentes genotóxicos. Dessa forma, sua ocorrência reflete o grau de exposição celular a carcinógenos. O objetivo deste trabalho foi avaliar a freqüência de micronúcleos em células esfoliadas da língua e da mucosa jugal de indiví-duos dependentes químicos de etanol. A amostra constou de células esfoliadas da língua e da mucosa jugal de 40 indivíduos alcoólatras não fumantes e de 20 abstêmios de álcool e fumo. As células obtidas foram coradas pelo método de Feulgen e contracoradas pelo "Fast Green". Observou-se um aumento estatisticamente significativo da freqüência de micronúcleos em células esfoliadas da língua no grupo de indivíduos expostos ao etanol em relação ao grupo controle (p < 0,01). A freqüência de micronúcleos em células esfoliadas da mucosa jugal apresentou-se maior no grupo de indivíduos alcoólatras quando comparado ao grupo controle, porém não houve diferença estatisticamente significante (p > 0,05). Conclui-se, portanto, que o consumo excessivo de etanol promove alterações efetivas em células da mucosa bucal, mesmo na ausência de exposição ao fumo. Tais alterações apresentam-se mais expressivas no bordo lateral de língua, um sítio mais exposto à ação de carcinógenos quando comparado à mucosa jugal. UNITERMOS: Neoplasias bucais; Etanol; Micronúcleos.ABSTRACT: Ethanol is one of the chemicals related to the development of oral malignant neoplasms. Micronuclei are chromatin fragments which, after aberrant mitoses, do not become included in the main nucleus. They have been used as indicators of genotoxic damage in cells exposed to carcinogens. The aim of this study was to assess the frequency of micronuclei in exfoliated cells from the tongue and buccal mucosa of alcoholic individuals. Samples were taken from the tongue and buccal mucosa of 40 alcoholic individuals who did not smoke, and from 20 alcohol and tobacco abstainers. Cells were stained with the Feulgen reaction and counterstained with Fast Green. A significant increase in the frequency of micronuclei in tongue cells was found in the group of subjects exposed to alcohol, when compared to the control group (p < 0.01). The frequency of micronuclei in buccal mucosa cells was higher in the group of alcoholic individuals, when compared to the control group, although there was no significant difference (p > 0.05). Our results indicate that excessive alcohol consumption may induce effective alterations on oral mucosa cells, even without exposure to tobacco. These alterations are more expressive in the tongue, which is a site more exposed to the action of carcinogens, when compared to the buccal mucosa. UNITERMS: Mouth neoplasms; Ethanol; Micronuclei. INTRODUÇÃODiversos agentes influem de forma genotóxica nas células e estão relacionados aos vários está-gios da carcinogênese. Com relação à cavidade bucal, o fumo tem sido descr...

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Section: Discussionunclassified

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Efeito genotóxico do etanol em células da mucosa bucal

Reis

Sadigursky

Andrade

et al. 2002

Pesqui. Odontol. Bras.

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“…However, little is known on the effect of zinc concentration on epithelial cells within the buccal mucosa. Buccal cells can be easily obtained in a minimally invasive manner and have been used extensively in human in vivo studies investigating the genotoxic effects of environmental and lifestyle factors (Nersesyan and Chobanyan 2010;Nersesyan 2006;Nersesyan and Adamyan 2004;Li et al 1998;Munoz et al 1987;Piyathilake et al 1995;Prasad et al 1995;Ramirez and Saldanha 2002;Thomas et al 2010). Determining the nutritional requirements for optimal genome integrity in human tissue is a high priority for disease prevention as risk for developmental and degenerative diseases increases with elevated rates of genetic damage (Fenech 2010).…”

Section: Introductionmentioning

confidence: 99%

Zinc deficiency or excess within the physiological range increases genome instability and cytotoxicity, respectively, in human oral keratinocyte cells

et al. 2011

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Zinc (Zn) is an essential component of Zn-finger proteins and acts as a cofactor for enzymes required for cellular metabolism and in the maintenance of DNA integrity. The study investigated the genotoxic and cytotoxic effects of Zn deficiency or excess in a primary human oral keratinocyte cell line and determined the optimal concentration of two Zn compounds (Zn Sulphate (ZnSO 4 ) and Zn Carnosine (ZnC)) to minimise DNA damage. Zn-deficient medium (0 lM) was produced using Chelex treatment, and the two Zn compounds ZnSO 4 and ZnC were tested at concentrations of 0.0, 0.4, 4.0, 16.0, 32.0 and 100.0 lM. Cell viability was decreased in Zndepleted cells (0 lM) as well as at 32 lM and 100 lM for both Zn compounds (P \ 0.0001) as measured via the MTT assay. DNA strand breaks, as measured by the comet assay, were found to be increased in Zn-depleted cells compared with the other treatment groups (P \ 0.05). The Cytokinesis Block Micronucleus Cytome assay showed a significant increase in the frequency of both apoptotic and necrotic cells under Zn-deficient conditions (P \ 0.05). Furthermore, elevated frequencies of micronuclei (MNi), nucleoplasmic bridges (NPBs) and nuclear buds (NBuds) were observed at 0 and 0.4 lM Zn, whereas these biomarkers were minimised for both Zn compounds at 4 and 16 lM Zn (P \ 0.05), suggesting these concentrations are optimal to maintain genome stability. Expression of PARP, p53 and OGG1 measured by western blotting was increased in Zn-depleted cells indicating that DNA repair mechanisms are activated. These results suggest that maintaining Zn concentrations within the range of 4-16 lM is essential for DNA damage prevention in cultured human oral keratinocytes.

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“…Although Se was not a single agent in these trials, it is likely to have been the most effective component, particularly in the light of subsequent studies (Wei et al 2004). (As one of a number of agents in an Indian trial Se has also been shown to aid the remission of precancerous lesions of the oral cavity Prasad et al 1995).) Hepatocellular carcinoma is highly prevalent in China.…”

Section: Intervention Studies Including Randomised Controlled Trialsmentioning

confidence: 99%

Selenium in cancer prevention: a review of the evidence and mechanism of action

2005

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Se is an unusual trace element in having its own codon in mRNA that specifies its insertion into selenoproteins as selenocysteine (SeCys), by means of a mechanism requiring a large SeCysinsertion complex. This exacting insertion machinery for selenoprotein production has implications for the Se requirements for cancer prevention. If Se may protect against cancer, an adequate intake of Se is desirable. However, the level of intake in Europe and some parts of the world is not adequate for full expression of protective selenoproteins. The evidence for Se as a cancer preventive agent includes that from geographic, animal, prospective and intervention studies. Newly-published prospective studies on oesophageal, gastric-cardia and lung cancer have reinforced previous evidence, which is particularly strong for prostate cancer. Interventions with Se have shown benefit in reducing the risk of cancer incidence and mortality in all cancers combined, and specifically in liver, prostate, colo-rectal and lung cancers. The effect seems to be strongest in those individuals with the lowest Se status. As the level of Se that appears to be required for optimal effect is higher than that previously understood to be required to maximise the activity of selenoenzymes, the question has been raised as to whether selenoproteins are involved in the anti-cancer process. However, recent evidence showing an association between Se, reduction of DNA damage and oxidative stress together with data showing an effect of selenoprotein genotype on cancer risk implies that selenoproteins are indeed implicated. The likelihood of simultaneous and consecutive effects at different cancer stages still allows an important role for anti-cancer Se metabolites such as methyl selenol formed from g-glutamyl-selenomethyl-SeCys and selenomethyl-SeCys, components identified in certain plants and Se-enriched yeast that have anti-cancer effects. There is some evidence that Se may affect not only cancer risk but also progression and metastasis. Current primary and secondary prevention trials of Se are underway in the USA, including the Selenium and Vitamin E Cancer Prevention Trial (SELECT) relating to prostate cancer, although a large European trial is still desirable given the likelihood of a stronger effect in populations of lower Se status.

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Micronuclei and carcinogen DNA adducts as intermediate end points in nutrient intervention trial of precancerous lesions in the oral cavity

Cited by 44 publications

References 16 publications

Efeito genotóxico do etanol em células da mucosa bucal

Efeito genotóxico do etanol em células da mucosa bucal

Zinc deficiency or excess within the physiological range increases genome instability and cytotoxicity, respectively, in human oral keratinocyte cells

Selenium in cancer prevention: a review of the evidence and mechanism of action

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