Radiation-induced mitotic catastrophe in FANCD2 primary fibroblasts
Апстракт
Purpose: As the Fanconi anemia (FA) pathway is required for appropriate cell cycle progression through mitosis and the completion of cell division, the aim of the present study was to determine the destiny of FA cells after irradiation in vitro and to elucidate any difference in radiosensitivity between FA and control cells. Materials and methods: Analyses of phosphorylated histone H2AX (gamma-H2AX) foci, micronuclei formation and cell cycle analysis were performed in unirradiated (0 min) and irradiated primary FA fibroblasts and in a control group at different post-irradiation times (30 min, 2 h, 5 h and 24 h). Results: The accumulation of gamma-H2AX foci in irradiated FA fibroblasts was observed. At 24 h post-irradiation, 57% of FA cells were gamma-H2AX foci-positive, significantly higher than in the control (p LT 0.01). The cell cycle analysis has shown the transient G2/M arrest in irradiated FA fibroblasts. The portion of cells in the G2/M phase showed initial increase at 30 min po...st-irradiation and afterwards decreased over time reaching the pretreatment level 24 h after irradiation. Irradiated FA fibroblasts progressed to abnormal mitosis, as is shown by the production of cells with different nuclear morphologies from binucleated to multinucleated surrounded with micronuclei, and also by a high percentage of foci-positive micronuclei. The majority of radiation-induced micronuclei were gamma-H2AX foci-positive, indicating that radiation-induced micronuclei contain fragments of damaged chromosomes. In contrast, in the control group, most of the micronuclei were classified as gamma-H2AX foci-negative, which indicates that cells with unrepaired damage were blocked before entering mitosis. Conclusion: The results clearly indicate that mitotic catastrophe might be an important cell-death mechanism involved in the response of FA fibroblasts to ionizing radiation.
Кључне речи:
Fanconi anemia / ionizing irradiation / gamma-H2AX / micronuclei / mitotic catastropheИзвор:
International Journal of Radiation Biology, 2014, 90, 5, 373-381Финансирање / пројекти:
- Радиосензитивност хуманог генома (RS-MESTD-Basic Research (BR or ON)-173046)
DOI: 10.3109/09553002.2014.892224
ISSN: 0955-3002; 1362-3095
PubMed: 24512567
WoS: 000335447700006
Scopus: 2-s2.0-84899878264
Колекције
Институција/група
VinčaTY - JOUR AU - Leskovac, Andreja AU - Petrović, Sandra AU - Guć-Šćekić, Marija AU - Vujić, Dragana AU - Joksić, Gordana PY - 2014 UR - https://vinar.vin.bg.ac.rs/handle/123456789/5986 AB - Purpose: As the Fanconi anemia (FA) pathway is required for appropriate cell cycle progression through mitosis and the completion of cell division, the aim of the present study was to determine the destiny of FA cells after irradiation in vitro and to elucidate any difference in radiosensitivity between FA and control cells. Materials and methods: Analyses of phosphorylated histone H2AX (gamma-H2AX) foci, micronuclei formation and cell cycle analysis were performed in unirradiated (0 min) and irradiated primary FA fibroblasts and in a control group at different post-irradiation times (30 min, 2 h, 5 h and 24 h). Results: The accumulation of gamma-H2AX foci in irradiated FA fibroblasts was observed. At 24 h post-irradiation, 57% of FA cells were gamma-H2AX foci-positive, significantly higher than in the control (p LT 0.01). The cell cycle analysis has shown the transient G2/M arrest in irradiated FA fibroblasts. The portion of cells in the G2/M phase showed initial increase at 30 min post-irradiation and afterwards decreased over time reaching the pretreatment level 24 h after irradiation. Irradiated FA fibroblasts progressed to abnormal mitosis, as is shown by the production of cells with different nuclear morphologies from binucleated to multinucleated surrounded with micronuclei, and also by a high percentage of foci-positive micronuclei. The majority of radiation-induced micronuclei were gamma-H2AX foci-positive, indicating that radiation-induced micronuclei contain fragments of damaged chromosomes. In contrast, in the control group, most of the micronuclei were classified as gamma-H2AX foci-negative, which indicates that cells with unrepaired damage were blocked before entering mitosis. Conclusion: The results clearly indicate that mitotic catastrophe might be an important cell-death mechanism involved in the response of FA fibroblasts to ionizing radiation. T2 - International Journal of Radiation Biology T1 - Radiation-induced mitotic catastrophe in FANCD2 primary fibroblasts VL - 90 IS - 5 SP - 373 EP - 381 DO - 10.3109/09553002.2014.892224 ER -
@article{ author = "Leskovac, Andreja and Petrović, Sandra and Guć-Šćekić, Marija and Vujić, Dragana and Joksić, Gordana", year = "2014", abstract = "Purpose: As the Fanconi anemia (FA) pathway is required for appropriate cell cycle progression through mitosis and the completion of cell division, the aim of the present study was to determine the destiny of FA cells after irradiation in vitro and to elucidate any difference in radiosensitivity between FA and control cells. Materials and methods: Analyses of phosphorylated histone H2AX (gamma-H2AX) foci, micronuclei formation and cell cycle analysis were performed in unirradiated (0 min) and irradiated primary FA fibroblasts and in a control group at different post-irradiation times (30 min, 2 h, 5 h and 24 h). Results: The accumulation of gamma-H2AX foci in irradiated FA fibroblasts was observed. At 24 h post-irradiation, 57% of FA cells were gamma-H2AX foci-positive, significantly higher than in the control (p LT 0.01). The cell cycle analysis has shown the transient G2/M arrest in irradiated FA fibroblasts. The portion of cells in the G2/M phase showed initial increase at 30 min post-irradiation and afterwards decreased over time reaching the pretreatment level 24 h after irradiation. Irradiated FA fibroblasts progressed to abnormal mitosis, as is shown by the production of cells with different nuclear morphologies from binucleated to multinucleated surrounded with micronuclei, and also by a high percentage of foci-positive micronuclei. The majority of radiation-induced micronuclei were gamma-H2AX foci-positive, indicating that radiation-induced micronuclei contain fragments of damaged chromosomes. In contrast, in the control group, most of the micronuclei were classified as gamma-H2AX foci-negative, which indicates that cells with unrepaired damage were blocked before entering mitosis. Conclusion: The results clearly indicate that mitotic catastrophe might be an important cell-death mechanism involved in the response of FA fibroblasts to ionizing radiation.", journal = "International Journal of Radiation Biology", title = "Radiation-induced mitotic catastrophe in FANCD2 primary fibroblasts", volume = "90", number = "5", pages = "373-381", doi = "10.3109/09553002.2014.892224" }
Leskovac, A., Petrović, S., Guć-Šćekić, M., Vujić, D.,& Joksić, G.. (2014). Radiation-induced mitotic catastrophe in FANCD2 primary fibroblasts. in International Journal of Radiation Biology, 90(5), 373-381. https://doi.org/10.3109/09553002.2014.892224
Leskovac A, Petrović S, Guć-Šćekić M, Vujić D, Joksić G. Radiation-induced mitotic catastrophe in FANCD2 primary fibroblasts. in International Journal of Radiation Biology. 2014;90(5):373-381. doi:10.3109/09553002.2014.892224 .
Leskovac, Andreja, Petrović, Sandra, Guć-Šćekić, Marija, Vujić, Dragana, Joksić, Gordana, "Radiation-induced mitotic catastrophe in FANCD2 primary fibroblasts" in International Journal of Radiation Biology, 90, no. 5 (2014):373-381, https://doi.org/10.3109/09553002.2014.892224 . .