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      Effects of age, sex, medication, and environmental conditions on genetic alterations in oral mucosa cells

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          Abstract

          In the present study, we evaluated the effects of biological factors, lifestyle factors, and environmental conditions on the induction of DNA damage in exfoliated cells of the oral mucosa. Age, sex, medication use, and environmental conditions were analyzed in individuals residing in the cities of Caarapó and Itaporã. The individuals were assessed by a questionnaire, and oral mucosa cells were collected and subjected to mutagenicity analysis. We observed no statistical differences in DNA damage related to sex. However, the mutagenic effect was found to be proportional to age, with higher frequencies of DNA damage observed in individuals between the ages of 46 and 65 years. In addition, higher frequencies of DNA damage were found in individuals who continuously used medication and for prolonged periods, and greater DNA damage was observed in individuals who used antihypertensive drugs than those who took antidepressants. In terms of environmental conditions, Caarapó residents had a significantly higher frequency of DNA damage than that of residents from Itaporã. Based on the analysis of land use and occupation, this result can be attributed to the smaller fraction of forest fragments and the higher proportion of buildings in Caarapó than Itaporã. We concluded that age, continued medication use, and environmental conditions can lead to greater DNA damage.

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          Buccal micronucleus cytome assay.

          Siegfried Knasmueller, Michael Fenech, Stefano Bonassi … (2008)
          The Buccal Micronucleus Cytome (BMCyt) assay is a minimally invasive method for studying DNA damage, chromosomal instability, cell death and the regenerative potential of human buccal mucosal tissue. This method is increasingly used in molecular epidemiological studies for investigating the impact of nutrition, lifestyle factors, genotoxin exposure and genotype on DNA damage, chromosome malsegregation and cell death. The biomarkers measured in this assay have been associated with increased risk of accelerated ageing, cancer and neurodegenerative diseases. This protocol describes one of the current established methods for buccal cell collection using a small-headed toothbrush, the generation of a single-cell suspension, slide preparation using cytocentrifugation, fixation and staining using Feulgen and Light Green for both bright field and fluorescence microscopic analysis. The scoring criteria for micronuclei and other nuclear anomalies are also described in detail. The protocol in its current form takes approximately 4 h to complete from the time of buccal cell collection to the generation of stained slides for microscopic analysis.
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            Micronuclei frequency in peripheral blood lymphocytes and cancer risk: evidence from human studies.

            Michael Fenech, Claudia Bolognesi, Stefano Bonassi … (2010)
            Over a century ago, Theodor Boveri paved the way to mechanistic studies linking chromosomal abnormalities to cancer pathogenesis. Since then, theoretical and empirical evidence has been accumulated, supporting a causal role of these events in the aetiology of human cancer. A powerful tool for measurement of chromosomal abnormalities is the cytokinesis-block micronucleus cytome (CBMNcyt) assay. The validation of the micronucleus (MN) as marker of phenotypic susceptibility to cancer has received decisive support from mutagens sensitivity studies, particularly from a recent case-control study on lung cancer, which showed increased frequency of tobacco carcinogen-induced MN, nuclear buds and especially nucleoplasmic bridges in cancer patients (odds ratios of 2.3, 10.0 and 45.5, respectively). Recently, a large international cohort study showed a significant association between MN frequency in healthy subjects and cancer risk. The study assembled data on 6718 individuals from 10 countries (62,980 person-years). Cancers incidence was significantly higher in groups with medium (RR=1.84; 95% confidence interval: 1.28-2.66) and high MN frequency (RR=1.53; 95% CI: 1.04-2.25). This study provided preliminary evidence that MN frequency in peripheral blood lymphocytes is predictive of cancer risk, suggesting that increased MN formation is associated with early events in carcinogenesis. These results, in combination with mechanistic evidence, prospected the use of MN frequency in cancer screening programmes. However, issues such as interindividual variability and preventive strategies in high-risk groups need to be further addressed to consolidate these achievements.
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              The effect of age, gender, diet and lifestyle on DNA damage measured using micronucleus frequency in human peripheral blood lymphocytes.

              Michael Fenech, Stefano Bonassi (2011)
              Micronucleus (MN) frequency in cytokinesis-blocked peripheral blood lymphocytes (PBL) has become one of the best-established biomarkers for studying DNA damage occurring in vivo in humans. The application of this method in population biomonitoring studies requires a deep understanding of how lifestyle and common host variables may influence MN frequency in PBL. In this mini-review, an update is provided on results from studies reporting on the impact of age, gender, diet and lifestyle factors (e.g. exercise, alcohol, smoking and recreational drugs) on this biomarker. Evidence from these studies shows that each of these factors, either in isolation or in combination, can significantly influence MN frequency. Proper control for these factors is required to enable better measurement of the impact of other conditions, such as environmental exposure to genotoxins or a susceptible genetic background, on MN frequency in PBL.
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                Author and article information

                Contributors
                Alexeia Barufatti
                Journal
                Journal ID (nlm-ta): Heliyon
                Journal ID (iso-abbrev): Heliyon
                Title: Heliyon
                Publisher: Elsevier
                ISSN (Electronic): 2405-8440
                Publication date PMC-release: 10 June 2019
                Publication date Collection: June 2019
                Publication date (Electronic): 10 June 2019
                Volume: 5
                Issue: 6
                Electronic Location Identifier: e01840
                Affiliations
                [a ]Faculdade de Ciências Biológicas e Ambientais, Universidade Federal da Grande Dourados, Rodovia Dourados – Itahum, Km 12 – Cidade Universitaria, Cx. Postal 364, CEP 79804-970, Dourados, MS, Brazil
                [b ]Universidade Estadual de Maringá, Av. Colombo, 5790 – Jd. Universitário, CEP 87020-900, Maringá, PR, Brazil
                [c ]Universidade Estadual do Mato Grosso do Sul, Rodovia Dourados – Itahum, Km 12 – Cidade Universitaria, Cx. Postal 351, CEP 79804-970, Dourados, MS, Brazil
                Author notes
                [∗ ]Corresponding author. barufattialexeia@ 123456gmail.com
                Article
                Publisher ID: S2405-8440(19)31743-8 Publisher ID: e01840
                DOI: 10.1016/j.heliyon.2019.e01840
                PMC ID: 6626306
                SO-VID: 63a3833c-5fb3-4247-a189-c08949a20829
                Copyright © © 2019 Published by Elsevier Ltd.
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 15 February 2019
                Date revision received : 21 May 2019
                Date accepted : 24 May 2019
                Categories
                Subject: Article

                Keywords: karyorrhexis,land use and coverage,mutagenesis,micronucleus,pharmaceutical drugk,genetics
                Data availability:
                Keywords: karyorrhexis, land use and coverage, mutagenesis, micronucleus, pharmaceutical drugk, genetics

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