Role of base-excision repair in the treatment of childhood acute lymphoblastic leukaemia with 6-mercaptopurine and high doses of methotrexate

Stańczyk, Małgorzata; Śliwiński, Tomasz; Trelińska, Joanna; Cuchra, Magda; Markiewicz, Łukasz; Dziki, Łukasz; Bieniek, Andrzej; Bielecka-Kowalska, Anna; Kowalski, Michał; Pastorczak, Agata; Szemraj, Janusz; Młynarski, Wojciech; Majsterek, Ireneusz

doi:10.1016/j.mrgentox.2011.10.009

Cited by 11 publications

(6 citation statements)

References 32 publications

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“…A similar concept has recently been presented by Stanczyk et al, who, by using a similar methodology to the present study, report significantly lower BER efficiency in lymphocytes taken from children suffering from childhood acute lymphoblastic leukemia in comparison to healthy controls [ 36 ]. Although CRC and leukemia are virtually incomparable due to their totally different natures, the BER system was found to play a crucial role in both and may also be involved in the pathogenesis of several other diseases.…”

Section: Discussionsupporting

confidence: 74%

Efficiency of Base Excision Repair of Oxidative DNA Damage and Its Impact on the Risk of Colorectal Cancer in the Polish Population

Kabziński

Mucha

Cuchra

et al. 2015

Oxidative Medicine and Cellular Longevity

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DNA oxidative lesions are widely considered as a potential risk factor for colorectal cancer development. The aim of this work was to determine the role of the efficiency of base excision repair, both in lymphocytes and in epithelial tissue, in patients with CRC and healthy subjects. SNPs were identified within genes responsible for steps following glycosylase action in BER, and patients and healthy subjects were genotyped. A radioisotopic BER assay was used for assessing repair efficiency and TaqMan for genotyping. Decreased BER activity was observed in lymphocyte extract from CRC patients and in cancer tissue extract, compared to healthy subjects. In addition, polymorphisms of EXO1, LIG3, and PolB may modulate the risk of colorectal cancer by decreasing (PolB) or increasing (LIG3 and EXO1) the chance of malignant transformation.

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Section: Discussionsupporting

confidence: 74%

Efficiency of Base Excision Repair of Oxidative DNA Damage and Its Impact on the Risk of Colorectal Cancer in the Polish Population

Kabziński

Mucha

Cuchra

et al. 2015

Oxidative Medicine and Cellular Longevity

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“…For example, MTX selectively led to cell death depending on the presence of defects in DNA mismatch repair 13. The defects in DNA base excision repair played a positive role in the MTX treatment of acute lymphoblastic leukemia 16. However, the role of unbalanced DNA damage and repair in the MTX sensitivity of choriocarcinoma remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Methotrexate induces DNA damage and inhibits homologous recombination repair in choriocarcinoma cells

Xie

Zhao

Cai

et al. 2016

OTT

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ObjectiveThe objective of this study was to investigate the mechanism of sensitivity to methotrexate (MTX) in human choriocarcinoma cells regarding DNA damage response.MethodsTwo choriocarcinoma cancer cell lines, JAR and JEG-3, were utilized in this study. An MTX-sensitive osteosarcoma cell line MG63, an MTX-resistant epithelial ovarian cancer cell line A2780 and an MTX-resistant cervical adenocarcinoma cell line Hela served as controls. Cell viability assay was carried out to assess MTX sensitivity of cell lines. MTX-induced DNA damage was evaluated by comet assay. Quantitative reverse transcription polymerase chain reaction was used to detect the mRNA levels of BRCA1, BRCA2, RAD51 and RAD52. The protein levels of γH2AX, RAD 51 and p53 were analyzed by Western blot.ResultsRemarkable DNA strand breaks were observed in MTX-sensitive cell lines (JAR, JEG-3 and MG63) but not in MTX-resistant cancer cells (A2780 and Hela) after 48 h of MTX treatment. Only in the choriocarcinoma cells, the expression of homologous recombination (HR) repair gene RAD51 was dramatically suppressed by MTX in a dose- and time-dependent manner, accompanied with the increase in p53.ConclusionThe MTX-induced DNA strand breaks accompanied by deficiencies in HR repair may contribute to the hypersensitivity to chemotherapy in choriocarcinoma.

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“…The comet assay is used in all constituent papers of this thesis, both without enzymes (papers I-IV), with FPG (papers I-IV) and with UDG (paper III). As far as I am aware, only a handful studies have previously used the UDG in the comet assay in human biomonitoring samples [85][86][87].…”

Section: The Comet Assaymentioning

confidence: 99%

The Effect of Sea Buckthorn Supplement on Oral Health, Inflammation, and DNA Damage in Hemodialysis Patients: A Double-Blinded, Randomized Crossover Study

Rodhe¹,

Woodhill²,

Thorman³

et al. 2013

Journal of Renal Nutrition

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Role of base-excision repair in the treatment of childhood acute lymphoblastic leukaemia with 6-mercaptopurine and high doses of methotrexate

Cited by 11 publications

References 32 publications

Efficiency of Base Excision Repair of Oxidative DNA Damage and Its Impact on the Risk of Colorectal Cancer in the Polish Population

Efficiency of Base Excision Repair of Oxidative DNA Damage and Its Impact on the Risk of Colorectal Cancer in the Polish Population

Methotrexate induces DNA damage and inhibits homologous recombination repair in choriocarcinoma cells

The Effect of Sea Buckthorn Supplement on Oral Health, Inflammation, and DNA Damage in Hemodialysis Patients: A Double-Blinded, Randomized Crossover Study

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