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Age-related changes in radiation-induced micronuclei among healthy adults

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      Abstract

      The aim of the present study was to establish the extent of in vitro radioresponse of lymphocytes among 62 healthy adults of both genders and to estimate the distribution of baseline micronuclei and radiosensitivity among individuals of the study population using the cytochalasin block micronucleus test. A younger study group consisted of 10 males (mean age, 22.4 years; range, 21-27) and 12 females (mean age, 24.8 years; range, 20-29), whereas an older study group consisted of 18 males (mean age, 35.1 years; range, 30-44) and 22 females (mean age, 38.5 years; range, 30-48). For evaluation of radiosensitivity blood samples were irradiated in vitro using 60Co g-ray source. The radiation dose employed was 2 Gy, the dose rate 0.45 Gy/min. The study revealed a significant gender effect on baseline micronuclei favoring females (Z = 3.25, P < 0.001), while yields of radiation-induced micronuclei did not differ significantly (Z = 0.56, P < 0.56) between genders. The distribution of baseline micronuclei among the individuals tested followed Poisson distribution in both study groups and in both genders, whereas the distribution of radiosensitivity among individuals of the older study group did not fulfill Poisson expectations (Kolmogorov-Smirnof test, P < 0.01). In contrast to a nonsignificant difference in radiosensitivity between males and females of the same age group (Z = 1.97, P < 0.56), a statistically significant difference in radiosensitivity between younger and older group for both genders was found (Z = 3.03, P < 0.03). Since the individuals tested were healthy, the observed variability in radiation response is considered to be an early effect of ageing.

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      The cytokinesis-block micronucleus technique: a detailed description of the method and its application to genotoxicity studies in human populations.

       M Fenech (1992)
      The development of the cytokinesis-block (CB) technique has transformed the human-lymphocyte micronucleus assay (MN) into a reliable and precise method for assessing chromosome damage. Recent studies in our laboratory have confirmed that this method is a sensitive indicator of in vivo radiation exposure in (a) patients undergoing fractionated partial-body radiotherapy and (b) rodents exposed to uniform whole-body irradiation, thus supporting the application of the cytokinesis-block micronucleus (CBMN) assay for biological dosimetry. To further define the use of this assay in biomonitoring we performed extensive studies to determine the spontaneous level of MN in normal human populations and its relationship to various life-style factors. We have also developed a new variation to the CBMN assay that permits the conversion of excision-repairable lesions to MN within one cell-cycle using cytosine arabinoside. With this method the slope of the in vitro dose-response curves was increased by a factor of 1.8 for X-rays, 10.3 for ultraviolet (UV, 254 nm) radiation and approximately 40-fold for methylnitrosourea. Consequently the CBMN assay can now be used to measure not only whole chromosome loss or chromosome breaks but also excision-repair events. The versatility and simplicity of the CBMN assay together with new developments in automation should ensure its successful application in monitoring exposed populations as well as in identifying mutagen-sensitive individuals within a population.
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        Biomarkers of genetic damage for cancer epidemiology.

        Cancer is a disease of altered gene expression involving a complex array of epigenetic events, gene mutation, chromosome rearrangements and altered chromosome number. The coincidence of genotoxic events with the induction of cancer has fueled great interest in molecular/cytogenetic epidemiological studies aimed at linking polymorphisms in genes for DNA repair and carcinogen metabolism and biomarkers of DNA/chromosome damage with cancer risk. These studies are now being expanded to include the role of dietary factors that are known to be important in DNA metabolism and repair such as folic acid, vitamin B12 and zinc. The use of DNA damage biomarkers as a surrogate for cancer would greatly facilitate our capacity to identify the most important risk factors for cancer however these biomarkers need validation. The Nordic and Italian prospective cohort studies have confirmed that elevated rates of chromosome aberrations in lymphocytes are predictive of cancer risk and similar studies are now underway to validate other biomarkers such as the micronucleus assay which are more practical to apply in the larger population setting. Validation of these biomarkers requires a thorough understanding of the importance of methodological, demographic, environmental and dietary variables and the ongoing HUMN project is a good example how this can be achieved for the micronucleus assay. The capacity to study human populations has opened up new opportunities to define acceptable DNA damage rates and to establish recommended dietary allowances for genomic stability. Controlling DNA damage rate to its possible minimum is likely to have an important impact in preventing cancer and other DNA damage-related degenerative diseases including ageing.
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          The use of the micronucleus test on exfoliated cells to identify anti-clastogenic action in humans: a biological marker for the efficacy of chemopreventive agents.

           Jessica Rosin (1992)
          Laboratory and epidemiological studies support the hypothesis that cancer incidence in human populations can be reduced by supplementing high-risk individuals with chemopreventive agents. Many candidate agents have been identified, too many to be assayed in long-term clinical trials. As an alternate approach, intermediate markers are currently being evaluated as short-term screens for the activity of chemopreventive agents in humans. These markers quantify cellular and molecular changes of biological significance to the process of carcinogenesis. One such marker is the micronucleus test on exfoliated cells. This assay has been used to quantify chromosomal breakage occurring in the human oral cavity, esophagus, cervix, lung, nasal cavity and urinary bladder. Intervention trials on high-risk populations have shown that supplementation with chemopreventive agents can modulate this breakage. This article will review the evidence in support of the use of this assay as a biological marker for the efficacy of a chemopreventive regime. Basic problem areas in the design and conduct of this assay in humans will also be discussed, as will the future potential of the assay.
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            Author and article information

            Affiliations
            [1 ] Vinca Institute of Nuclear Sciences Yugoslavia
            Contributors
            Role: ND
            Role: ND
            Role: ND
            Journal
            bjmbr
            Brazilian Journal of Medical and Biological Research
            Braz J Med Biol Res
            Associação Brasileira de Divulgação Científica (Ribeirão Preto )
            1414-431X
            August 2004
            : 37
            : 8
            : 1111-1117
            S0100-879X2004000800002
            10.1590/S0100-879X2004000800002

            http://creativecommons.org/licenses/by/4.0/

            Product
            Product Information: SciELO Brazil
            Categories
            BIOLOGY
            MEDICINE, RESEARCH & EXPERIMENTAL

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