In vivo γ-rays Induced Initial DNA Damage and the Effect of Famotidine in Mouse Leukocytes as Assayed by the Alkaline Comet Assay

Mozdarani, Hossein; Nasirian, Borzo; Haeri, S. Abolghasem

doi:10.1269/jrr.06055

Cited by 18 publications

(7 citation statements)

References 20 publications

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“…Thus, there is first an increase and then a decrease in the SSB that the alkaline comet assay detects. The strict time-dependency of the level achieved by the radio-induced DNA lesions (Mozdarani et al 2007) is fully supported by the present data. As a consequence, the present conclusions should only be valid for the relatively short time of recovery used throughout this study (2 h).…”

Section: Discussionsupporting

confidence: 87%

Hepatocytes, rather than leukocytes reverse DNA damage in vivo induced by whole body y-irradiation of mice, as shown by the alkaline comet assay

et al. 2008

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BRHepatocytes, rather than leukocytes reverse DNA damage in vivo induced by whole body γ-irradiation of mice, as shown by the alkaline comet assay DNA damage repair was assessed in quiescent (G 0 ) leukocytes and in hepatocytes of mice, after 1 and 2 hours recovery from a single whole body γ-irradiation with 0.5, 1 or 2 Gy. Evaluation of single-strand breaks (SSB) and alkali-labile sites together were carried out by a single-cell electrophoresis at pH>13.0 (alkaline comet assay). In non-irradiated (control) mice, the constitutive, endogenous DNA damage (basal) was around 1.5 times higher in leukocytes than in hepatocytes. Irradiation immediately increased SSB frequency in both cell types, in a dose-dependent manner. Two sequential phases took place during the in vivo repair of the radioinduced DNA lesions. The earliest one, present in both hepatocytes and leukocytes, further increased the SSB frequency, making evident the processing of some primary lesions in DNA bases into the SSB repair intermediates. In a second phase, SSB frequency decreased because of their removal. In hepatocytes, such a frequency regressed to the constitutive basal level after 2 hours recovery from either 0.5 or1 Gy. On the other hand, the SSB repair phase was specifically abrogated in leukocytes, at the doses and recovery times analyzed. Thus, the efficiency of in vivo repair of radio-induced DNA damage in dormant cells (lymphocytes) is quite different from that in hepatocytes whose low proliferation activity accounts only for cell renewal.

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Section: Discussionsupporting

confidence: 87%

Hepatocytes, rather than leukocytes reverse DNA damage in vivo induced by whole body y-irradiation of mice, as shown by the alkaline comet assay

et al. 2008

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“…For example, the repair of DNA DSBs may influence the dose assessment results derived from the comet assay because in real-life situations, victims of radiation exposure are likely to be tested at various times after the exposure has occurred. Therefore, DNA repair kinetics after irradiation should always be assessed by the comet assay [26]. …”

Section: Resultsmentioning

confidence: 99%

Evaluation of the Comet Assay for Assessing the Dose-Response Relationship of DNA Damage Induced by Ionizing Radiation

Wang

et al. 2013

IJMS

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Dose- and time-response curves were combined to assess the potential of the comet assay in radiation biodosimetry. The neutral comet assay was used to detect DNA double-strand breaks in lymphocytes caused by γ-ray irradiation. A clear dose-response relationship with DNA double-strand breaks using the comet assay was found at different times after irradiation (p < 0.001). A time-response relationship was also found within 72 h after irradiation (p < 0.001). The curves for DNA double-strand breaks and DNA repair in vitro of human lymphocytes presented a nice model, and a smooth, three-dimensional plane model was obtained when the two curves were combined.

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“…This response has already been demonstrated in MDA-MB-231 and may result from DNA damage induced by reactive oxygen species generated by IR [4,19]. DNA single-and double-strand breaks may occur after treatment with IR and this activates DNA repair systems [5].…”

Section: Discussionmentioning

confidence: 80%

“…Radiotherapy uses ionizing radiation and induces the formation of reactive oxygen species, which damage different cellular components including proteins, the cell membrane, and DNA [4]. Double-strand breaks are the most common alterations observed in DNA after exposure to IR.…”

Section: Introductionmentioning

confidence: 99%

Effect of radiation treatment on newly established human breast cancer cell lines MACL-1 and MGSO-3

et al. 2010

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The characterization of new cell lines is an important tool to understand the biological processes involved in cancer treatments. In the present study, we used two newly established epithelial human breast cancer cell lines from primary sites MACL-1 and MGSO-3 and compared their susceptibility to the treatment with ionizing radiation (IR) with the commercial cell line MDA-MB-231. In the doses used (10 or 20 Gy), IR induced a reduction in cell viability and cell death, measured as DNA fragmentation, at 48 and 72 h after treatment. In addition, 48 h after treatment with IR, we observed an enhancement in the percentage of apoptotic cells. The broad-range caspases inhibitor zVAD-FMK inhibited cytotoxicity induced by IR. After 24 h, treatment with IR activated caspase-9 in MACL-1 and MDA-MB-231 but not in MGSO-3 cells. Thirty hours after treatment with IR (20 Gy), we observed an activation of caspases 8 and 3. These results suggest the involvement of caspases in the cell death induced by IR in two newly established cell lines. These cells may be useful in studies of breast cancer in defining basic mechanisms in molecular and cellular radiobiology and may contribute to the rational design of future models of cancer therapies.

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In vivo γ-rays Induced Initial DNA Damage and the Effect of Famotidine in Mouse Leukocytes as Assayed by the Alkaline Comet Assay

Cited by 18 publications

References 20 publications

Hepatocytes, rather than leukocytes reverse DNA damage in vivo induced by whole body y-irradiation of mice, as shown by the alkaline comet assay

Hepatocytes, rather than leukocytes reverse DNA damage in vivo induced by whole body y-irradiation of mice, as shown by the alkaline comet assay

Evaluation of the Comet Assay for Assessing the Dose-Response Relationship of DNA Damage Induced by Ionizing Radiation

Effect of radiation treatment on newly established human breast cancer cell lines MACL-1 and MGSO-3

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