• The Journal of Natural Sciences
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• v.8 no.2
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• pp.43-48
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• 1996

Mutangen sensitive hyper-rec type musN mutants were assigned into the UvsC group which contains genes involved in recombination and mutation. however, phenotypic properties of musN mutants were very different from those found in uvsC mutant strains which are rec- and lack UV-induced mutation. musN was not a mutator like uvsC. In addition, selenate resistant mutations in musN were induced sililar to those in wild types by UV irradiation. Wild type levels of UV-sensitivity in dividing cells of musN also differ from the uvsC phenotypes. These indicate that the UvsC group has branched pathways.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3417-3422
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• 2012

Objective: Non-homologous end joining (NHEJ) is one of the pathways of repair of DNA double-strand breaks. A number of genes involved in NHEJ have been implicated as breast cancer susceptibility genes such as LIG4. However, some studies have generated conflicting results. The aim of this Human Genome Epidemiology (HuGE) review and meta-analysis was to investigate association between LIG4 gene polymorphisms in the NHEJ pathway and breast cancer risk. Methods: Studies focusing on the relationship between LIG4 gene polymorphisms and susceptibility to breast cancer were selected from the Pubmed, Cochrane library, Embase, Web of Science, Springerlink, CNKI and CBM databases. Data were extracted by two independent reviewers and the meta-analysis was performed with Review Manager Version 5.1.6 and STATA Version 12.0 software, calculating odds ratios (ORs) with 95% confidence intervals (95%CIs). Results: According to the inclusion criteria, we final included seven studies with a total of 10,321 breast cancer cases and 10,160 healthy controls in the meta-analysis. The results showed no association between LIG4 gene polymorphisms (rs1805386 T>C, rs1805389 C>T, rs1805388 C>T and rs2232641 A>G) and breast cancer risk, suggesting that the mutant situation of these SNPs neither increased nor decreased the risk for breast cancer. In the subgroup analysis by Hardy-Weinberg equilibrium (HWE) and ethnicity, we also found no associations between the variants of LIG4 gene and breast cancer risk among HWE, non-HWE, Caucasians, Asians and Africans. Conclusion: This meta-analysis suggests that there is a lack of any association between LIG4 gene polymorphisms and the risk of breast cancer.

• Journal of Microbiology and Biotechnology
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• v.26 no.12
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• pp.2106-2115
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• 2016

To identify the global effects of (p)ppGpp in the gram-positive bacterium Deinococcus radiodurans, which exhibits remarkable resistance to radiation and other stresses, RelA/SpoT homolog (RSHs) mutants were constructed by direct deletion mutagenesis. The results showed that RelA has both synthesis and hydrolysis domains of (p)ppGpp, whereas RelQ only synthesizes (p)ppGpp in D. radiodurans. The growth assay for mutants and complementation analysis revealed that deletion of relA and relQ sensitized the cells to $H_2O_2$, heat shock, and amino acid limitation. Comparative proteomic analysis revealed that the bifunctional RelA is involved in DNA repair, molecular chaperone functions, transcription, the tricarboxylic acid cycle, and metabolism, suggesting that relA maintains the cellular (p)ppGpp levels and plays a crucial role in oxidative resistance in D. radiodurans. The D. radiodurans relA and relQ genes are responsible for (p)ppGpp synthesis/hydrolysis and (p)ppGpp hydrolysis, respectively. (p)ppGpp integrates a general stress response with a targeted re-programming of gene regulation to allow bacteria to respond appropriately towards heat shock, oxidative stress, and starvation. This is the first identification of RelA and RelQ involvement in response to oxidative, heat shock, and starvation stresses in D. radiodurans, which further elucidates the remarkable resistance of this bacterium to stresses.

• Development and Reproduction
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• v.17 no.1
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• pp.63-72
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• 2013

A specific inhibitor of RNA polymerase II, ${\alpha}$-amanitin is broadly used to block transcriptional activities in cells. Previous studies showed that ${\alpha}$-amanitin affects in vitro maturation of cumulus-oocyte-complex (COC). In this study, we evaluated the target of ${\alpha}$-amanitin, and whether it affects oocytes or cumulus cells (CCs), or both. We treated ${\alpha}$-amanitin with different time period during in vitro culture of denuded oocytes (DOs) or COCs in comparison, and observed the changes in morphology and maturation status. Although DOs did not show any change in morphology and maturation rates with ${\alpha}$-amanitin treatment, oocytes from COCs were arrested at metaphase I (MI) stage and CCs were more scattered than control groups. To discover causes of meiotic arrest and scattering of CCs, we focused on changes of cumulus expansion, gap junctions, and cellular metabolism which to be the important factors for the successful in vitro maturation of COCs. Expression of genes for cumulus expansion markers (Ptx3, Has2, and Tnfaip6) and gap junctional proteins (Gja1, Gja4, and Gjc1) decreased in ${\alpha}$-amanitin-treated CCs. However, these changes were not observed in oocytes. In addition, expression of genes related to metabolism (Prps1, Rpe, Rpia, Taldo1, and Tkt) decreased in ${\alpha}$-amanitin-treated CCs but not in oocytes. Therefore, we concluded that the transcriptional activities of CCs for supporting suitable transcripts, especially for its metabolic activities and formation of gap junctions among CCs as well as with oocytes, are important for oocytes maturation in COCs.

• Journal of Korean Biological Nursing Science
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• v.20 no.2
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• pp.55-66
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• 2018

Purpose: Peripheral neuropathy is common among colorectal cancer (CRC) patients who undergo oxaliplatin-based (OXL) chemotherapy. A pharmacogenetic approach can be used to identify patients at high-risk of developing severe neuropathy. This type of approach can also help clinicians determine the best treatment option and prevent severe neurotoxicity. The purpose of this study is to investigate the evidence of pharmacogenetic markers for OXL-induced peripheral neuropathy (OXIPN) in patients with CRC. Methods: A systematic literature search was conducted using the following databases up to December 2017: Pubmed, EMBASE, and CINAHL. We reviewed the genetic risk factors for OXIPN in observational studies and randomized controlled clinical trials (RCTs). All processes were performed independently by two reviewers. Results: Sixteen studies published in English between 2006 and 2017 were included in this review. A genome-wide association approach was used in one study and various candidate genes were tested, based on their functions (e.g., DNA damage or repair, ion channels, anti-oxidants, and nerve growth etc.). The genes associated with incidence or severity of OXIPN were ABCG2, GSTP1, XRCC1, TAC1, and ERCC1. Conclusion: This study highlighted the need and the importance of conducting pharmacogenetic studies to generate evidence of personalized OXIPN symptoms management. Additional studies are warranted to accelerate the tailored interventions used for OXIPN in patients with CRC (NRF-2014R1A1A3054386).

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.6
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• pp.2811-2819
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• 2016

Multiple genetic and environmental factors have been reported to play key role in the development of nasopharyngeal carcinoma (NPC). Here, we investigated interactions of XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms and environmental factors in modulating susceptibility to NPC in Northeast India. One-hundred NPC patients, 90 first-degree relatives of patients and 120 controls were enrolled in the study. XRCC1 Arg399Gln and XRCC2 Arg188His polymorphisms were determined using PCR-RFLP, and the results were confirmed by DNA sequencing. Logistic regression (LR) and multifactor dimensionality reduction (MDR) approaches were applied for statistical analysis. The XRCC1 Gln/Gln genotype showed increased risk (OR=2.76; P<0.024) of NPC. However, individuals with both XRCC1 and XRCC2 polymorphic variants had 3.2 fold elevated risk (P<0.041). An enhanced risk of NPC was also observed in smoked meat (OR=4.07; P=0.004) and fermented fish consumers (OR=4.34, P=0.001), and tobacco-betel quid chewers (OR=7.00; P=0.0001) carrying XRCC1 polymorphic variants. However, smokers carrying defective XRCC1 gene showed the highest risk (OR = 7.47; P<0.0001). On MDR analysis, the best model for NPC risk was the five-factor model combination of XRCC1 variant genotype, fermented fish, smoked meat, smoking and chewing (CVC=10/10; TBA=0.636; P<0.0001); whereas in interaction entropy graphs, smoked meat and tobacco chewing showed synergistic interactions with XRCC1. These findings suggest that interaction of genetic and environmental factors might increase susceptibility to NPC in Northeast Indian populations.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.8
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• pp.4107-4111
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• 2016

Background: Oral cancers account for approximately 2% of all cancers diagnosed each year; however, the vast majority (80%) of the affected individuals are smokers whose risk of developing a lesion is five to nine times greater than that of non-smokers. Tobacco smoke contains numerous carcinogens that cause DNA damage, including oxidative lesions that are removed effectively by the base-excision repair (BER) pathway, in which poly (ADP-ribose) polymerase 1 (PARP-1), plays key roles. Genetic variations in the genes encoding DNA repair enzymes may alter their functions. Several studies reported mixed effects on the association between PARP-1 variants and the risk of cancer development. Till now no reported studies have investigated the association between PARP-1 variants and oral squamous cell carcinoma (OSCC) risk in an Indian population. Materials and Methods: In the present case control study 100 OSCC patients and 100 matched controls were genotyped using PARP1 single nucleotide peptides (SNP's) rs1136410 and rs3219090 using TaqMan assays. Results: The results indicated significantly higher risk with PARP1 rs1136410 minor allele "C" (OR=1.909; p=0.02942; CI, 1.060-3.439). SNP rs1136410 also showed significantly increased risk in patients with smoking habit at C/C genotype and at minor allele C. Conclusions: The PAPR-1 Ala762Val polymorphism may play a role in progression of OSCC. Larger studies with a greater number of samples are needed to verify these findings.

• The Journal of Korean Obstetrics and Gynecology
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• v.23 no.2
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• pp.38-56
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• 2010

Purpose: This study was designed to evaluate the effect of administration of Foeniculi Fructus on ovarian functions and differential gene expressions related cell viability such as caspase-3, MAPK and MPG in female mice. Methods: We administered the Foeniculi Fructus to 6-week-old female CF-1 mice for 4, 8, 12 days. After administration of Foeniculi Fructus with 0.1, 1, 10, $100\;mg/m{\ell}$ concentration in the comparison of control group with $0\;mg/m{\ell}$, we observed the mean number of total ovulated oocytes and the number of morphologically normal oocytes. After entosomatic fertilization, we observed the rate of fertilized 2-cell embryos to blastocyst stage in vitro. Also we chose the caspase-3 for cell apoptosis, MAPK and MPG genes for cell viability and DNA repair by RT-PCR. Results: 1. In case of 4, 8, 12day administration of Foeniculi Fructus with 0.1, 1, 10, $100\;mg/m{\ell}$, the mean number of total ovulated oocytes and the number of morphologically normal oocytes were increased in the comparison of control group. 2. In case of 4, 8, 12day administration of Foeniculi Fructus with 0.1, 1, 10, $100\;mg/m{\ell}$, the rates of blastocyst formation from 2-cell stages were increased in the comparison of control group. 3. In case of 4, 8, 12day administration of Foeniculi Fructus with 0.1, 1, 10, $100\;mg/m{\ell}$, the gene expression of caspase-3, MAPK, MPG didn't show significant result in the comparison of control group. Conclusion: This study shows that Foeniculi Fructus has significant effects on the increase of the function on ovulation and embryonic development of female mice. But this results have nothing to do with caspase-3, MAPK and MPG genes. So we need a further study for which genes are related to the activation of reproductive functions of Foeniculi Fructus.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.11
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• pp.6721-6726
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• 2013

Background: Changes in DNA methylation patterns are believed to be early events in hepatocarcinogenesis. A better understanding of methylation states and how they correlate with disease progression will aid in finding potential strategies for early detection of HCC. The aim of our study was to analyze the methylation frequency of tumor suppressor genes, P14, P15, and P73, and a mismatch repair gene (O6MGMT) in HCV related chronic liver disease and HCC to identify candidate epigenetic biomarkers for HCC prediction. Materials and Methods: 516 Egyptian patients with HCV-related liver disease were recruited from Kasr Alaini multidisciplinary HCC clinic from April 2010 to January 2012. Subjects were divided into 4 different clinically defined groups - HCC group (n=208), liver cirrhosis group (n=108), chronic hepatitis C group (n=100), and control group (n=100) - to analyze the methylation status of the target genes in patient plasma using EpiTect Methyl qPCR Array technology. Methylation was considered to be hypermethylated if >10% and/or intermediately methylated if >60%. Results: In our series, a significant difference in the hypermethylation status of all studied genes was noted within the different stages of chronic liver disease and ultimately HCC. Hypermethylation of the P14 gene was detected in 100/208 (48.1%), 52/108 (48.1%), 16/100 (16%) and 8/100 (8%) among HCC, liver cirrhosis, chronic hepatitis and control groups, respectively, with a statistically significant difference between the studied groups (p-value 0.008). We also detected P15 hypermethylation in 92/208 (44.2%), 36/108 (33.3%), 20/100 (20%) and 4/100 (4%), respectively (p-value 0.006). In addition, hypermethylation of P73 was detected in 136/208 (65.4%), 72/108 (66.7%), 32/100 (32%) and 4/100 (4%) (p-value <0.001). Also, we detected O6MGMT hypermethylation in 84/208 (40.4%), 60/108 (55.3%), 20/100 (20%) and 4/100 (4%), respectively (p value <0.001. Conclusions: The epigenetic changes observed in this study indicate that HCC tumors exhibit specific DNA methylation signatures with potential clinical applications in diagnosis and prognosis. In addition, methylation frequency could be used to monitor whether a patient with chronic hepatitis C is likely to progress to liver cirrhosis or even HCC. We can conclude that methylation processes are not just early events in hepatocarcinogenesis but accumulate with progression to cancer.

• Radiation Oncology Journal
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• v.24 no.1
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• pp.30-36
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• 2006

Purpose: It is well known from clinical experience that acute complications of chemoradiation therapy vary from patients to patients. However, there are no known factors to predict these acute complications before treatment starts. The human XRCC1 gene is known as a DNA base excision repair gene. We investigated the possibilities of XRCC1 gene polymorphisms as a predictor for the acute complications of chemoradiation therapy in colorectal cancer patients. Materials and Methods: From July 1997 to June 2003, 86 colorectal cancer patients (71 rectal cancer, 13 sigmoid colon cancer and 2 colon cancer patients) were treated with chemoradiation therapy at the Department of Radiation Oncology, Inha University Hospital. Twenty-two patients were in stage B, 50 were in stage C, 8 were in stage D and 6 patients were unresectable cases. External radiation therapy was delivered with 10MV X-ray at a 1.8 Gy fraction per day for a total dose of radiation of $30.6{\sim}59.4 Gy$ (median: 54 Gy). All the patients received 5-FU based chemotherapy regimen. We analyzed the acute complications of upper and lower gastrointestinal tract based on the RTOG complication scale. The initial and lowest WBC and platelet count were recorded during both the RT period and the whole treatment period. Allelic variants of the XRCC1 gene at codons 194, 280 and 399 were analyzed in the lymphocyte DNA by performing PCR-RFLP. Statistical analyses were carried out with the SAS (version 6.12) statistical package. Results: When all the variables were assessed on the multivariate analysis, recurrent disease revealed the factors that significantly correlated with upper gastrointestinal acute complications. Arg399Gln polymorph isms of the XRCC1 gene, the radiation dose and the frequencies of chemotherapy during radiation therapy were significantly correlated with lower gastrointestinal complications. Arg399Gln polymorph isms also affected the decrease of the WBC and platelet count during radiation therapy. Conclusion: Although the present sample size was too small for fully evaluating this hypothesis, this study suggests that Arg399Gln polymorph isms of the XRCC1 genes may be used as one of the predictors for acute complications of chemoradiation therapy in colorectal cancer patients.