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Boric acid as a protector against paclitaxel genotoxicity

100%
Turkez H., Tatar A., Hacımuftuoglu A., Ozdemir E.
Acta Biochimica Polonica
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2010
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vol. 57
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issue 1
95-97
EN
Paclitaxel (PAC) is an anticancer drug used for treatments of breast, ovarian and lung cancers. However, little data is available in the literature on its potential genotoxicity on healthy human cells. On the other hand, boron deficiency and supplementation exert important biological effects in human and animal tissues. The biological effects of dietary boron are defined, but its interaction with PAC is not known for therapeutic uses. The aim of the present study was to determine whether boric acid (BA) confer a protection against PAC genotoxicity. After the application of PAC (10 or 20 µg/l) and BA (2.5 or 5 mg/l), the genotoxic effects were assessed by sister chromatid exchange (SCE) and micronucleus (MN) tests in human blood cultures. We also analyzed nuclear division index (NDI) in peripheral lymphocytes. Our results showed that PAC significantly (P<0.05) increased the frequencies of SCEs and the formations of MNs in peripheral lymphocytes as compared to controls. PAC decreased the nuclear division index in lymphocyte cultures. Boric acid did not show cytotoxic or genotoxic effects at the concentrations tested. Furthermore, the PAC-induced increases in the genotoxicity and cytotoxicity indices were diminished by the addition of BA. The present study suggests for the first time that BA can prevent the genotoxicity of PAC on human lymphocytes.
2
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Biomarkers used to assess radio- and chemotherapy-induced lymphocyte genome instability in a case of cerebral infarction during relapse of a testicular seminoma

86%
Gamulin M., Pastuhović A., Šantek F., Grgić M., Kopjar N.
Biomonitoring
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2014
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vol. 1
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issue 1
EN
We report a case of a testicular seminoma patient with relapse who was irradiated after acute cerebral infarction induced by cisplatin-based chemotherapy. Lymphocytic genome instability was studied using an alkaline comet assay, analysis of structural chromosome aberrations, and cytokinesis-block micronucleus assay in blood samples collected before and after PET CT scanning that preceded radiotherapy, as well as before the administration of the first and after the administration of the last fraction of 3D conformal radiation. A challengetest with hydrogen peroxide (H2O2) was performed on isolated peripheral blood lymphocytes in order to establish to what extent earlier therapies had modified the response of the patient’s DNA to external stimuli with a genotoxic chemical. Levels of primary DNA damage in lymphocytes increased after diagnostic exposure, lowered prior to administration of a conformal 3D radiotherapy, and were the highest at the end of radiotherapy. Ex vivo exposure to H2O2 caused additional lymphocyte DNA damage, which gradually increased 15 and 30 minutes after treatment. Diagnostic and therapeutic exposure to radiation caused measurable cytogenetic damage that was subjected to extensive repair. All of the obtained results point to increased genomic instability in the patient which should be taken into account in his future medical surveillance.
3
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Correlation between folate and vitamin B12 and markers of DNA stability in healthy men: preliminary results

86%
Milić M., Rozgaj R., Kašuba V., Oreščanin V., Balija M., Jukić I.
Acta Biochimica Polonica
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2010
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vol. 57
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issue 3
339-345
EN
The aim of this study was to find correlations between folate and vitamin B12 on baseline damage in white blood cells and their association with smoking, alcohol consumption and ageing. Thirty-six healthy vitamin non-deficient male subjects were selected in a randomized study. Comet assay (SCGE) and micronucleus (MN) assay were used as biomarkers of DNA damage. The amount of DNA damage was correlated with vitamin B12 and folic acid concentration. Positive, but non-significant correlation (canonical R = 0.61; χ2=28.97; P=0.253) was found between micronucleus (MN) frequency or comet assay parameters (SCGE) and five covariates (age, smoking, alcohol consumption, vitamin B12 and folate blood serum concentration). The highest MN frequency was observed in the group with the lowest vitamin B12 concentration (F=3.59; P=0.024). The SCGE assay failed to show significant correlation with vitamin B12 or folic acid concentration. Concentration of vitamin B12 was significantly correlated with incidence of micronuclei. Our results present background data that could be valuable for future genotoxicological monitoring.
4
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Antimutagenic effects of aqueous fraction of Myristica fragrans (Houtt.) leaves on Salmonella typhimurium and Mus musculus

86%
Akinboro A., Bin Mohamed K., Asmawi M., Yekeen T.
Acta Biochimica Polonica
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2014
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vol. 61
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issue 4
779-785
EN
Natural plant extracts offer a promising hope in the prevention/treatment of cancer arising from genetic mutations. This study evaluated in vitro and in vivo mutagenic and antimutagenic effects of aqueous fraction of Myristica fragrans (AFMF) leaves on TA100 strain of Salmonella typhimurium and Mus musculus (Male Swiss albino mice), respectively. The antioxidant activity of AFMF against 2,2-diphenyl-1-picrylhydrazyl (DPPH), total phenolic and flavonoid contents were determined, followed by its phytochemical elucidation using the Ultra Performance Liquid Chromatography technique (UPLC). The mutagenicity of AFMF at 4, 20, 50, 100, 200, 500, and 1000 µg/well was <2.0 in S. typhimurium and the induced micronucleated polychromatic and normochromatic erythrocytes at 500, 1000, 2000, and 4000 mg/kg were not significantly different from the negative control (p≥0.05). The mutagenic activity of benzo[a]pyrene and cyclophosphamide was significantly suppressed above 50.0% throughout the tested concentrations. Fifty percent of the free radicals from DPPH were scavenged by AFMF at 0.11 mg/ml. Total phenolic and flavonoid contents of AFMF were 51.0 mg GAE/g and 27 mg QE/g, respectively. Rutin was elucidated by the UPLC technique, and thereby suspected to be the phytochemical responsible for the observed antimutagenic activity. Thus far, AFMF seems to contain a promising chemotherapeutic agent for the prevention of genetic damage that is crucial for cancer development.
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