The Fanconi anemia pathway and DNA interstrand cross-link repair

Su, Xiaoyu

doi:10.1007/s13238-011-1098-y

Cited by 34 publications

(41 citation statements)

References 86 publications

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“…Both Fancd2 −/− and heterozygote Fancd2 +/− mice were radiosensitive to head and neck irradiation compared to control Fancd2 +/+ mice measured as oral cavity tissue ulceration at day 5 postirradiation. These results confirm and extend previous publications showing radiosensitivity of total-body-irradiated Fancd2 −/− mice and the critical role of the Fancd2 protein in the response to the radiation injury (9–13, 16, 25–28). Intraoral JP4-039/F15 protected normal tissues in head and neck irradiated Fancd2 −/− mice as well as control Fancd2 +/+ mice.…”

Section: Discussionsupporting

confidence: 92%

Amelioration of Radiation-Induced Oral Cavity Mucositis and Distant Bone Marrow Suppression in Fanconi Anemia Fancd2–/– (FVB/N) Mice by Intraoral GS-Nitroxide JP4-039

et al. 2014

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The altered DNA damage response pathway in patients with Fanconi anemia (FA) may increase the toxicity of clinical radiotherapy. We quantitated oral cavity mucositis in irradiated Fanconi anemia Fancd2−/− mice, comparing this to Fancd2+/− and Fancd2+/+ mice, and we measured distant bone marrow suppression and quantitated the effect of the intraoral radioprotector GS-nitroxide, JP4-039 in F15 emulsion. We found that FA mice were more susceptible to radiation injury and that protection from radiation injury by JP4-039/F15 was observed at all radiation doses. Adult 10–12-week-old mice, of FVB/N background Fancd2−/−, Fancd2+/− and Fancd2+/+ were head and neck irradiated with 24, 26, 28 or 30 Gy (large fraction sizes typical of stereotactic radiosurgery treatments) and subgroups received intraoral JP4-039 (0.4 mg/mouse in 100 μL F15 liposome emulsion) preirradiation. On day 2 or 5 postirradiation, mice were sacrificed, tongue tissue and femur marrow were excised for quantitation of radiation-induced stress response, inflammatory and antioxidant gene transcripts, histopathology and assay for femur marrow colony-forming hematopoietic progenitor cells. Fancd2−/− mice had a significantly higher percentage of oral mucosal ulceration at day 5 after 26 Gy irradiation (59.4 ± 8.2%) compared to control Fancd2+/+ mice (21.7 ± 2.9%, P = 0.0063). After 24 Gy irradiation, Fancd2−/− mice had a higher oral cavity percentage of tongue ulceration compared to Fancd2+/+ mice irradiated with higher doses of 26 Gy (P = 0.0123). Baseline and postirradiation oral cavity gene transcripts were altered in Fancd2−/− mice compared to Fancd2+/+ controls. Fancd2−/− mice had decreased baseline femur marrow CFU-GM, BFUe and CFU-GEMM, which further decreased after 24 or 26 Gy head and neck irradiation. These changes were not seen in head- and neck-irradiated Fancd2+/+ mice. In radiosensitive Fancd2−/− mice, biomarkers of both local oral cavity and distant marrow radiation toxicity were ameliorated by intraoral JP4-039/F15. We propose that Fancd2−/− mice are a valuable radiosensitive animal model system, which can be used to evaluate potential radioprotective agents.

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Section: Discussionsupporting

confidence: 92%

Amelioration of Radiation-Induced Oral Cavity Mucositis and Distant Bone Marrow Suppression in Fanconi Anemia Fancd2–/– (FVB/N) Mice by Intraoral GS-Nitroxide JP4-039

et al. 2014

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“…Mutations in FA pathway lead to a rare autosomal recessive disorder characterized by defects in all stages of ICL repair. 29,30 These repair defects are associated with congenital malformations, progressive bone marrow failure, profound genomic instability and a highly elevated risk of hematological malignancies and solid tumors. 31 The disease is genetically heterogeneous, and patients with mutations in 15 genes have been reported to show traits associated with FA (FANCA, B, C, D1/BRCA2, D2, E, F, G, H, I, J/BACH1/ BRIP1, L, M, N/PALB2, P/SLX4/ BTBD12 and O/RAD51C).…”

mentioning

confidence: 99%

A prototypical Fanconi anemia pathway in lower eukaryotes?

2012

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“…There are still some FA patients reported with unassigned subtypes, and it is suggested that the identification of additional FA or FA associated genes will give further insights into the molecular functions and mechanism of the FA pathway. 28 In conclusion, this study revealed that microphthalmia, thumb anomalies and café au lait spots are significantly more frequent in DEB/ MMC(+) cases. Anemia alone is not a determinate of FA.…”

Section: Discussionmentioning

confidence: 54%

An Evaluation of the Phenotypic Features of Fanconi Anemia Together with DEB/MMC Positivity in 199 Turkish Patients

Yurur-Kutlay¹,

Tuncali²,

Ilgin-Ruhi³

et al. 2013

Turkiye Klinikleri J Med Sci

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A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Fanconi anemia is a severe and progressive genetic disease characterized by pancytopenia, a broad range of congenital abnormalities and marked predisposition to malignancy. In this study, the relationship between the clinical manifestations and diepoxybutane/mitomycin C (DEB/MMC) test results was investigated in a group of patients. In particular, the diagnostic significance of minor phenotypic findings was evaluated. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : A total of 199 cases referred to our department with a diagnosis of Fanconi anemia between 1989 and 2004 were investigated retrospectively. Major and minor clinical findings specific to Fanconi anemia were evaluated in detail. The correlation between chromosomal break ratios occurring either spontaneously or with DEB/MMC induction in lymphocyte cultures from peripheral blood or bone marrow samples and the frequency of phenotypic findings were analyzed with chi-square test and logistic regression. R Re es su ul lt ts s: : Among 199 patients diagnosed with Fanconi anemia, 117 (58.8%) were DEB/MMC (+). Ocular abnormalities, mainly microphtalmia, [31 patients (26.5%) DEB/MMC (+) vs 2 patients (2.5%) DEB/MMC (-)] were the most significant finding followed by café au lait spots [67 patients (57.3%) DEB/MMC (+) vs 15 patients (18.3%) DEB/MMC (-)] and thumb anomalies [52 patients (44.5%) DEB/MMC (+) vs 8 patients (9.8%) DEB/MMC (-)] for the diagnosis of Fanconi anemia. In this study, the two major findings of Fanconi anemia, anemia and growth retardation did not contribute to the logistic regression model for the specific diagnosis of the disease. C Co on nc cl lu us si io on n: : Characteristic findings in Fanconi anemia may lead to diagnosis. However, in certain conditions where classical clinical manifestations are not present it would be particularly important to evaluate the individual malformations, which may be of value for the diagnosis of Fanconi anemia patients during the pre-anemia stage. K Ke ey y W Wo or rd ds s: : Fanconi anemia; phenotype; diagnosis; chromosome breakage Ö ÖZ ZE ET T A Am ma aç ç: : Fanconi anemisi pansitopeni, çeşitli konjenital anomaliler ve maliniteye yatkınlıkla karakterize ağır ve ilerleyici bir genetik hastalıktır. Hastalarda gözlenen klinik bulgular geniş bir yelpazede yer almaktadır. Bu çalışmada Fanconi anemisinin klinik bulguları diepoksibütan/mitomisin C (DEB/MMC) testi sonuçları ile birlikte analiz edilerek, fenotipik özellikler ile DEB/MMC testi sonuçları arasındaki ilişki araştırılmış, özellikle minör olarak tanımlanan fenotipik bulguların tanıdaki önemi değerlendirilmiştir. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : 1989-2004 yılları arasında bölümümüze Fanconi anemisi ön tanısı ile gönderilen 199 olgu geriye dönük olarak incelenmiştir. Fanconi anemisinde tanımlanan major ve minör fenotipik değişiklikler başta olmak üzere, hastaların fizik muayene bulguları ayrıntılı olarak incelenmiştir. Olguların periferik kan veya kemik iliği lenfosi...

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The Fanconi anemia pathway and DNA interstrand cross-link repair

Cited by 34 publications

References 86 publications

Amelioration of Radiation-Induced Oral Cavity Mucositis and Distant Bone Marrow Suppression in Fanconi Anemia Fancd2–/– (FVB/N) Mice by Intraoral GS-Nitroxide JP4-039

Amelioration of Radiation-Induced Oral Cavity Mucositis and Distant Bone Marrow Suppression in Fanconi Anemia Fancd2–/– (FVB/N) Mice by Intraoral GS-Nitroxide JP4-039

A prototypical Fanconi anemia pathway in lower eukaryotes?

An Evaluation of the Phenotypic Features of Fanconi Anemia Together with DEB/MMC Positivity in 199 Turkish Patients

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