Evaluation of genomic instability and cancer prevention
Keywords:
Antineoplastic agents, Down syndrome, Fanconi anemia, cytokinesis-block micronucleus assay, single-cell-gel electrophoresisAbstract
OBJECTIVES: This study aimed at verifying the damage index acquired from the environment and from an inherited condition in the leukocytes of workers occupationally exposed to Xradiation and antineoplastic drugs, patients with Down syndrome, Fanconi anemia, and controls.
MATERIAL AND METHODS: Cytokinesis-block micronucleus assay (CB-MN) and single-cell-gel electrophoresis (SCGE) were employed in 22 workers potentially exposed to X-radiation and 22 controls matched for age, sex, and smoking habits from a hospital in southern Brazil. The same evaluation was employed in 12 individuals who had been occupationally exposed to antineoplastic drugs and in 14 patients with Fanconi anemia (FA), 30 with Down syndrome (DS), and 30 controls,
in order to examine the sensitivity of the techniques to detect specific genome instability.
RESULTS: Both CB-MN and SCGE showed increased genetic damage in the cells of exposed individuals. In individuals handling antineoplastic drugs, no statistically difference was found when using CB-MN; however, the mean value of SCGE was significantly higher in exposed individuals when compared to controls. Down syndrome presented an increase just in the SCGE technique; the frequency of micronuclei and dicentric bridges was similar to that found in controls. Both CB-MN and SCGE showed increased genetic damage in the cells of individuals with Fanconi anemia. The high frequency of micronuclei seems to be due to clastogenic events, since the frequency of dicentric bridges was also elevated.
DISCUSSION: Both methods are efficient for monitoring mutagenic events in exposed populations or individuals presenting genetic instability. CB-MN represents a longer time of exposure, while SCGE detects momentary DNA damage and/or repair activity. The combination of both techniques is recommended to monitor chronically exposed populations. Changes in lifestyle may constitute an important way of preventing carcinogenesis, either in individuals presenting increased risk and in the general population.
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