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Case-only study of interactions between DNA repair genes (hMLH1, APEX1, MGMT, XRCC1 and XPD) and low-frequency electromagnetic fields in childhood acute leukemia.

A case-only study was conducted in 123 patients with sporadic acute leukemia (AL). The locations of electric transformers and power lines were noted in each area, and their distances from the houses of the study patients were measured. The intensities of magnetic fields (B) were measured in 66 cases. Unconditional logistic regression analysis was performed adjusting for age, gender, parental education and occupation, indoor and outdoor pesticides use, presence of television sets, refrigerators and microwave ovens in children's rooms and the presence of chemical factories or telecommunication t

Determinants of chemosensitivity in gastric cancer.

Recent advances in the management of gastric cancer, especially in the arena of chemotherapy, are paving the way for optimization of treatment that maximizes effectiveness while minimizing toxicity. The expansion of the chemotherapeutic armamentarium has led to multiple combinations of cytotoxic agents. Unfortunately, the benefit of chemotherapy has been modest at best, and no one combination has shown significant superiority over the others in comparative Phase III trials. It is in this setting that pharmacogenetic advances have the potential to play an important role in achieving superior cl

The DNA repair helicases XPD and FancJ have essential iron-sulfur domains.

DNA helicases are essential components of the cellular machinery for DNA replication, recombination, repair, and transcription. The XPD and FancJ proteins are related helicases involved in the nucleotide excision repair (NER) and Fanconi anemia repair pathways, respectively. We demonstrate that both proteins have a conserved domain near the N terminus that includes an iron-sulfur (Fe-S) cluster. Three absolutely conserved cysteine residues provide ligands for the Fe-S cluster, which is essential for the helicase activity of XPD. Yeast strains harboring mutations in the Fe-S domain of Rad3 (yea

Polymorphisms of the DNA repair genes XRCC1, XRCC3, XPD, interaction with environmental exposures, and bladder cancer risk in a case-control study in northern Italy.

Tobacco smoking and occupational exposures are the main known risk factors for bladder cancer, causing direct and indirect damage to DNA. Repair of DNA damage is under genetic control, and DNA repair genes may play a key role in maintaining genome integrity and preventing cancer development. Polymorphisms in DNA repair genes resulting in variation of DNA repair efficiency may therefore be associated with bladder cancer risk. A hospital-based case-control study was conducted in Brescia, Italy, to assess the relationship between polymorphisms in DNA repair genes XRCC1 (Arg(399)Gln), XRCC3 (Thr(2

Dimerization of human XPA and formation of XPA2-RPA protein complex.

XPA plays an important role in the DNA damage recognition during human nucleotide excision repair. Here we report that the XPA is a homodimer either in the free state or as a complex with human RPA in solution under normal conditions. The human XPA protein purified from baculovirus-infected sf21 insect cells has a molecular mass of 36 317 Da, as determined by mass spectroscopy. However, the apparent molecular mass of XPA determined by the native gel filtration chromatography was about 71 kDa, suggesting that XPA is a dimer. This observation was supported by a native PFO-PAGE and fluorescence s

Different dynamics in nuclear entry of subunits of the repair/transcription factor TFIIH.

We report here the different ways in which four subunits of the basal transcription/repair factor TFIIH (XPB, XPD, p62 and p44) and the damage recognition XPC repair protein can enter the nucleus. We examined their nuclear localization by transiently expressing the gene products tagged with the enhanced green fluorescent protein (EGFP) in transfected 3T3 cells. In agreement with the identification of more than one putative nuclear localization signal (NLS) in their protein sequences, XPB, XPC, p62 and p44 chimeras were rapidly sorted to the nucleus. In contrast, the XPD-EGFP chimeras appeared

Psoriasis patients with basal cell carcinoma have more repair-mediated DNA strand-breaks after UVC damage in lymphocytes than psoriasis patients without basal cell carcinoma.

We have investigated the formation of strand-breaks following UVC irradiation in lymphocytes from psoriasis patients with or without basal cell carcinoma (BCC). Isolated lymphocytes were irradiated with UVC light at a dose of 3.6 J/m(2), and the level of DNA strand-breaks were measured 25 min after the irradiation by the alkaline comet assay. The generation of strand-breaks following UVC irradiation indicates DNA-repair-mediated incisions, as UVC light does not generate strand-breaks per se. We found that psoriasis patients with BCC had more DNA-repair incisions than non-cancer patients. The i

Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells.

Polymorphisms in several DNA repair genes have recently been identified, but little is known about their phenotypic significance. To determine whether variation in DNA repair genes is related to host DNA damage, we studied the association between polymorphisms in XRCC1 (codon 399) and ERCC2 (codon 751) and two markers of DNA damage, sister chromatid exchange (SCE) frequencies (n = 76) and polyphenol DNA adducts (n = 61). SCE frequencies were determined using a modified fluorescence-Giemsa method and polyphenol DNA adducts were determined using a P1-enhanced (32)P-post-labeling procedure. XRCC1

PERIOCULAR HIGH RISK BCCS AFTER ADDITIONAL/PARALLEL INTAKE OF TORASEMIDE, MOXONIDINE AND MIRABEGRON: IMPORTANT LINKS TO SKIN CANCER RELATED (PHOTO-) NITROSOGENESIS IN THE CONTEXT OF PHARMACO-ONCOGENESIS.

The Nitrosogenesis of skin cancer is a modern newly introduced concept in medicine, mainly concerning melanoma, but also keratinocytic cance … intake of drugs), 3) congenital or acquired immunodeficiencies, and 4) Goltz Gorlin syndrome or 5) Xeroderma pigmentosum. Nitrosamines/ NDSRIs within the framework of polycotaminated drug intake appear to be one reasonable additional explanation for the association between carcinogen intake and subsequent skin cancer development and progression, and a relatively short …

Hypercalcemia of malignancy in metastatic esophageal squamous cell carcinoma with simultaneous PTHrP and calcitriol overproduction: A case report with literature review.

INTRODUCTION AND IMPORTANCE: hypercalcemia of malignancy is a severe complication of malignancy and associated with poor prognosis. Four mechanisms are implicated in this metabolic disorder, including excess parathyroid-related peptide secretion, focal osteolysis secondary to bone metastasis or multiple myeloma, excess calcitriol production, and ectopic parathyroid hormone production. Humoral hypercalcemia of malignancy secondary to isolated PTHrP or calcitriol overproduction is known; however, hypercalcemia of malignancy due to simultaneous PTHrP and calcitriol overproduction is less well kno

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… Zoledronate-responsive calcitriol-mediated hypercalcemia in a 5-year-old case with squamous cell carcinoma on the background of xeroderma pigmentosum. J. Pediatr. Endocrinol. Metab. 2019;32(12):1403–1406. doi: 10.1515/jpem-2019-0158. 11. Shivnani S.B. …

Pharmacological inhibition of cryptochrome and REV-ERB promotes DNA repair and cell cycle arrest in cisplatin-treated human cells.

Nucleotide excision repair (NER) and cell cycle checkpoints impact the ability of the anti-cancer drug cisplatin to inhibit cell proliferation and induce cell death. Genetic studies have shown that both NER and cell cycle progression are impacted by the circadian clock, which has emerged as a novel pharmacological target for the treatment of various disease states. In this study, cultured human cell lines were treated with combinations of cisplatin and the circadian clock modulating compounds KS15 and SR8278, which enhance circadian clock transcriptional output by inhibiting the activities of

Risk Modulation of Oral Pre Cancer and Cancer with Polymorphisms in XPD and XPG Genes in North Indian Population.

Background: Environmental carcinogens cause DNA damages which if not repaired properly, may increase the risk of cancer. The Xerodermapigmentosum group D (XPD) and group G (XPG) genes are essential genes for DNA repair and alteration in DNA repair causes cancer. The present study aimed to evaluate the relationship between XPD and XPG polymorphisms and risk of oral pre cancer and cancer. Methods: Present study genotyped 302 samples of oral diseases and 300 controls for XPD (A/C) and XPG (G/C) polymorphisms with PCR-RFLP method. Results: Our result showed that compared to AA genotype frequency o

Genetic variants of nucleotide excision repair pathway and outcomes of induction therapy in acute myeloid leukemia.

Aim: Acute myeloid leukemia (AML) is a heterogeneous disease in pathogenesis and response to therapy. Nucleotide excision repair (NER) pathway has a major role in the elimination of genotoxic effects of chemotherapeutic agents. We aimed to clarify the effects of selected variants of XPD, XPC, ERCC5 and ERCC1 genes on the outcomes of induction therapy. Materials & methods: The prevalence of NER genetic variants was evaluated in 67 subjects with AML and their effects on clinical outcomes were analyzed by χ2 test. Results: The XPD 751 Lys variant was associated with improved response to chemother

Combined effect of ERCC1 and ERCC2 polymorphisms on overall survival in non-squamous non-small-cell lung cancer patients treated with first-line pemetrexed/platinum.

OBJECTIVES: Polymorphisms of DNA repair genes may affect DNA repair capacity and the sensitivity of platinum doublets chemotherapy in non-small-cell lung cancer (NSCLC). We prospectively evaluated whether single nucleotide polymorphisms (SNPs) of ERCC1, ERCC2, XRCC1, and XRCC3 were associated with treatment outcome in advanced non-squamous NSCLC patients receiving pemetrexed/platinum as their first-line chemotherapy. MATERIALS AND METHODS: Genotyping of six SNPs in four DNA repair genes in 58 patients treated with first-line pemetrexed/platinum was performed using TaqMan SNP Genotyping Assays

Genetic risk of subsequent esophageal cancer in lymphoma and breast cancer long-term survival patients: a pilot study.

The occurrence of a second primary esophageal carcinoma (EC) in long-term cancer survivors may represent a late effect of previous radio-chemotherapeutic treatment. To identify the genetic factors that could increase this risk, we analyzed nine variants within ERCC1, XPD, XRCC1 and XRCC3 DNA repair pathway genes, and GSTP1, TP53 and MDM2 genes in 61 patients who received radio-chemotherapy for a prior lymphoma or breast cancer; 29 of them had a second primary EC. This cohort consists of 22 esophageal squamous cell carcinoma (ESCC) and 7 esophageal adenocarcinoma (EADC) patients. A validation c

Prognostic value of ERCC1 and ERCC2 gene polymorphisms in patients with gastric cancer receiving platinum-based chemotherapy.

We conducted a prospective study to analyze whether ERCC1 rs11615 and rs3212986 and ERCC2 rs13181 and rs1799793 gene polymorphisms could serve as potential biomarkers for the prognosis of gastric cancer. A total of 228 patients with pathologically proven gastric cancer and receiving platinum-based chemotherapy were recruited from our hospital between October 2009 and October 2011. The ERCC1 rs11615 and rs3212986 and ERCC2 rs13181 and rs1799793 polymorphisms were genotyped using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) assay. Conditional logistic regress

Strong expression of survivin is associated with positive response to radiotherapy and improved overall survival in head and neck squamous cell carcinoma patients.

Head and neck squamous cell carcinoma (HNSCC) is a malignancy that is associated with severe mortality despite advances in therapy. Today's standard treatment most commonly includes radiotherapy, often combined with chemotherapy or surgery. There are so far no established biomarkers to predict response to radiation, and thus the aim of this study was to investigate a series of markers that could potentially identify HNSCC patients who would benefit from radiotherapy. The selected markers, both proteins (epidermal growth factor receptor, survivin and p53), and single nucleotide polymorphisms (S

Exhaled ERCC-1 and ERCC-2 microsatellite alterations in NSCLC patients.

BACKGROUND: The excision repair cross-complementation (ERCC) enzyme plays a rate-limiting role in nucleotide excision repair pathway. Microsatellite alterations (MAs) at the long arm of chromosome 19, where are located the ERCC genes, have recently been associated with non-small cell lung cancer (NSCLC) pathogenesis and reduced survival. The aim of the present study was to explore MAs at 19q in DNA from exhaled breath condensate (EBC) of NSCLC patients investigating their possible correlation with the smoking habit, with the biological behaviour of the tumour and their predictive survival powe

Oxidative damage to biological macromolecules in Prague bus drivers and garagemen: impact of air pollution and genetic polymorphisms.

DNA integrity was investigated in the lymphocytes of 50 bus drivers, 20 garagemen and 50 controls using the comet assay with excision repair enzymes. In parallel, 8-oxo-7,8-dihydro-2'-deoxyguanosine and 15-F(2t)-isoprostane levels in the urine and protein carbonyl levels in the plasma were assessed as markers of oxidative damage to DNA, lipids and proteins. Exposure to carcinogenic polycyclic aromatic hydrocarbons (cPAHs) and volatile compounds was measured by personal samplers for 48 and 24h, respectively, before the collection of biological specimens. Both exposed groups exhibited a higher l