Abstract：
:Fanconi anemia (FA) is an inherited disorder characterized by defective DNA repair and cellular sensitivity to DNA crosslinking agents. Clinically, FA is associated with high risk for marrow failure, leukemia and head and neck squamous cell carcinoma (HNSCC). Radiosensitivity in FA patients compromises the use of total-body irradiation for hematopoietic stem cell transplantation and radiation therapy for HNSCC. A radioprotector for the surrounding tissue would therefore be very valuable during radiotherapy for HNSCC. Clonogenic radiation survival curves were determined for pre- or postirradiation treatment with the parent nitroxide Tempol or JP4-039 in cells of four FA patient-derived cell lines and two transgene-corrected subclonal lines. FancG(-/-) (PD326) and FancD2(-/-) (PD20F) patient lines were more sensitive to the DNA crosslinking agent mitomycin C (MMC) than their transgene-restored subclonal cell lines (both P < 0.0001). FancD2(-/-) cells were more radiosensitive than the transgene restored subclonal cell line (ñ = 2.0 ± 0.7 and 4.7 ± 2.2, respectively, P = 0.03). In contrast, FancG(-/-) cells were radioresistant relative to the transgene-restored subclonal cell line (ñ = 9.4 ± 1.5 and 2.2 ± 05, respectively, P = 0.001). DNA strand breaks measured by the comet assay correlated with radiosensitivity. Cell lines from a Fanc-C and Fanc-A patients showed radiosensitivity similar to that of Fanc-D2(-/-) cells. A fluorophore-tagged JP4-039 (BODIPY-FL) analog targeted the mitochondria of the cell lines. Preirradiation or postirradiation treatment with JP4-039 at a lower concentration than Tempol significantly increased the radioresistance and stabilized the antioxidant stores of all cell lines. Tempol increased the toxicity of MMC in FancD2(-/-) cells. These data provide support for the potential clinical use of JP4-039 for normal tissue radioprotection during chemoradiotherapy in FA patients.
journal_name
Radiat Resjournal_title
Radiation researchauthors
Bernard ME,Kim H,Berhane H,Epperly MW,Franicola D,Zhang X,Houghton F,Shields D,Wang H,Bakkenist CJ,Frantz MC,Forbeck EM,Goff JP,Wipf P,Greenberger JSdoi
10.1667/rr2624.1subject
Has Abstractpub_date
2011-11-01 00:00:00pages
603-12issue
5eissn
0033-7587issn
1938-5404pii
10.1667/RR2624.1journal_volume
176pub_type
杂志文章abstract：:Using atomic force microscopy (AFM), we have investigated neutron-induced DNA double-strand breaks in plasmids in aqueous solution. AFM permits direct measurement of individual DNA molecules with an accuracy of a few nanometers. Furthermore, the analysis of the DNA fragment size distribution is non-parametric, whereas...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1998-12-01 00:00:00
abstract：:It is well known that ionizing radiation-induced toxicity to normal tissue has functional consequences in the brain. However, the underlying molecular alterations have yet to be elucidated. We have previously reported cognitive impairments with concomitant changes in dendritic complexity, spine density and inflammatio...
journal_title：Radiation research
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doi：10.1667/RR15061.1
更新日期：2018-11-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RADE-20-00102.1
更新日期：2021-01-29 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3158
更新日期：2004-06-01 00:00:00
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doi：10.1667/RADE-20-00042.1
更新日期：2020-10-16 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1983-07-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/rr3360
更新日期：2005-05-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章,评审
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更新日期：2015-02-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1998-10-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1989-10-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR1469.1
更新日期：2009-02-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1988-11-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR14443.1
更新日期：2016-11-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1998-07-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/0033-7587(2000)154[0326:todiiq]2.0.co;2
更新日期：2000-09-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR15358.1
更新日期：2019-11-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1983-01-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1986-03-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1988-04-01 00:00:00
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journal_title：Radiation research
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更新日期：2019-05-01 00:00:00
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journal_title：Radiation research
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journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1985-12-01 00:00:00
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pub_type： 杂志文章
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更新日期：2017-01-01 00:00:00
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pub_type： 杂志文章
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更新日期：2014-07-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
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更新日期：2005-04-01 00:00:00
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journal_title：Radiation research
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更新日期：2017-06-01 00:00:00
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journal_title：Radiation research
pub_type： 杂志文章
doi：10.1667/RR1541.1
更新日期：2009-11-01 00:00:00
abstract：:Most plutonium-induced bone tumors in beagles arise in trabecular bone sites surrounded by hematopoietic tissue. The microvasculature and the relative incorporation of 241Pu (a low energy beta emitter) on trabecular bone surfaces from red and fatty marrow sites were studied in the adult beagle. The vascular volume, as...
journal_title：Radiation research
pub_type： 杂志文章
doi：
更新日期：1984-08-01 00:00:00
