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The Cellular Response to Oxidatively Induced DNA Damage and Polymorphism of Some DNA Repair Genes Associated with Clinicopathological Features of Bladder Cancer.

Savina NV, Nikitchenko NV, Kuzhir TD, Rolevich AI, Krasny SA, Goncharova RI - Oxid Med Cell Longev (2015)

Bottom Line: The study was aimed at evaluating the DNA damage response in H2O2-treated lymphocytes using the alkaline comet assay in bladder cancer (BC) patients as compared to clinically healthy controls, elderly persons, and individuals with chronic inflammations.The increased level of H2O2-induced DNA damage and a higher proportion of individuals sensitive to oxidative stress were found among BC patients as compared to other groups under study.The frequency of the XPD 312Asn allele was significantly higher in T ≥ 2 high grade than in T ≥ 2 low grade tumors (p = 0.036); the ERCC6 1097Val/Val genotype was strongly associated with muscle-invasive tumors.

View Article: PubMed Central - PubMed

Affiliation: Institute of Genetics and Cytology, National Academy of Sciences of Belarus, 27 Akademicheskaya Street, 220072 Minsk, Belarus.

ABSTRACT
Genome instability and impaired DNA repair are hallmarks of carcinogenesis. The study was aimed at evaluating the DNA damage response in H2O2-treated lymphocytes using the alkaline comet assay in bladder cancer (BC) patients as compared to clinically healthy controls, elderly persons, and individuals with chronic inflammations. Polymorphism in DNA repair genes involved in nucleotide excision repair (NER) and base excision repair (BER) was studied using the PCR-RFLP method in the Belarusian population to elucidate the possible association of their variations with both bladder cancer risk and clinicopathological features of tumors. The increased level of H2O2-induced DNA damage and a higher proportion of individuals sensitive to oxidative stress were found among BC patients as compared to other groups under study. Heterozygosity in the XPD gene (codon 751) increased cancer risk: OR (95% CI) = 1.36 (1.03-1.81), p = 0.031. The frequency of the XPD 312Asn allele was significantly higher in T ≥ 2 high grade than in T ≥ 2 low grade tumors (p = 0.036); the ERCC6 1097Val/Val genotype was strongly associated with muscle-invasive tumors. Combinations of homozygous wild type alleles occurred with the increased frequency in patients with non-muscle-invasive tumors suggesting that the maintenance of normal DNA repair activity may prevent cancer progression.

No MeSH data available.


Related in: MedlinePlus

The oxidatively induced DNA damage and DNA repair kinetics in isolated lymphocytes from BC patients as compared to healthy donors. The case group included 40 BC patients; the control group comprised 35 clinically healthy donors. The insert reflects the DNA repair kinetics on a logarithmic scale. The coefficients of linear regression in the groups of patients (β = −0.39) and controls (β = −0.36) are approximately equal.
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fig1: The oxidatively induced DNA damage and DNA repair kinetics in isolated lymphocytes from BC patients as compared to healthy donors. The case group included 40 BC patients; the control group comprised 35 clinically healthy donors. The insert reflects the DNA repair kinetics on a logarithmic scale. The coefficients of linear regression in the groups of patients (β = −0.39) and controls (β = −0.36) are approximately equal.

Mentions: To estimate adequately the cellular response to oxidized DNA damage in bladder cancer, it was compared among several groups and first of all between the cases and controls (Table 3, Figure 1). The results indicated the absence of statistically significant differences between the levels of basal DNA damage in the control and case groups, whereas the levels of H2O2-induced DNA damage in BC patients exceeded those in healthy volunteers during the whole period of observations. The greatest differences were observed immediately after lymphocyte mutagenic exposure. Nevertheless, the slopes of repair kinetics closely resembled each other (the insert in Figure 1), and, being compared by means of regression analysis, these data revealed no differences between two groups with respect to the DNA repair velocity. DNA repair efficiency was also equal in lymphocytes from patients and controls (Table 3), suggesting that induced DNA damage was eliminated in a similar manner in both groups.


The Cellular Response to Oxidatively Induced DNA Damage and Polymorphism of Some DNA Repair Genes Associated with Clinicopathological Features of Bladder Cancer.

Savina NV, Nikitchenko NV, Kuzhir TD, Rolevich AI, Krasny SA, Goncharova RI - Oxid Med Cell Longev (2015)

The oxidatively induced DNA damage and DNA repair kinetics in isolated lymphocytes from BC patients as compared to healthy donors. The case group included 40 BC patients; the control group comprised 35 clinically healthy donors. The insert reflects the DNA repair kinetics on a logarithmic scale. The coefficients of linear regression in the groups of patients (β = −0.39) and controls (β = −0.36) are approximately equal.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4663333&req=5

fig1: The oxidatively induced DNA damage and DNA repair kinetics in isolated lymphocytes from BC patients as compared to healthy donors. The case group included 40 BC patients; the control group comprised 35 clinically healthy donors. The insert reflects the DNA repair kinetics on a logarithmic scale. The coefficients of linear regression in the groups of patients (β = −0.39) and controls (β = −0.36) are approximately equal.
Mentions: To estimate adequately the cellular response to oxidized DNA damage in bladder cancer, it was compared among several groups and first of all between the cases and controls (Table 3, Figure 1). The results indicated the absence of statistically significant differences between the levels of basal DNA damage in the control and case groups, whereas the levels of H2O2-induced DNA damage in BC patients exceeded those in healthy volunteers during the whole period of observations. The greatest differences were observed immediately after lymphocyte mutagenic exposure. Nevertheless, the slopes of repair kinetics closely resembled each other (the insert in Figure 1), and, being compared by means of regression analysis, these data revealed no differences between two groups with respect to the DNA repair velocity. DNA repair efficiency was also equal in lymphocytes from patients and controls (Table 3), suggesting that induced DNA damage was eliminated in a similar manner in both groups.

Bottom Line: The study was aimed at evaluating the DNA damage response in H2O2-treated lymphocytes using the alkaline comet assay in bladder cancer (BC) patients as compared to clinically healthy controls, elderly persons, and individuals with chronic inflammations.The increased level of H2O2-induced DNA damage and a higher proportion of individuals sensitive to oxidative stress were found among BC patients as compared to other groups under study.The frequency of the XPD 312Asn allele was significantly higher in T ≥ 2 high grade than in T ≥ 2 low grade tumors (p = 0.036); the ERCC6 1097Val/Val genotype was strongly associated with muscle-invasive tumors.

View Article: PubMed Central - PubMed

Affiliation: Institute of Genetics and Cytology, National Academy of Sciences of Belarus, 27 Akademicheskaya Street, 220072 Minsk, Belarus.

ABSTRACT
Genome instability and impaired DNA repair are hallmarks of carcinogenesis. The study was aimed at evaluating the DNA damage response in H2O2-treated lymphocytes using the alkaline comet assay in bladder cancer (BC) patients as compared to clinically healthy controls, elderly persons, and individuals with chronic inflammations. Polymorphism in DNA repair genes involved in nucleotide excision repair (NER) and base excision repair (BER) was studied using the PCR-RFLP method in the Belarusian population to elucidate the possible association of their variations with both bladder cancer risk and clinicopathological features of tumors. The increased level of H2O2-induced DNA damage and a higher proportion of individuals sensitive to oxidative stress were found among BC patients as compared to other groups under study. Heterozygosity in the XPD gene (codon 751) increased cancer risk: OR (95% CI) = 1.36 (1.03-1.81), p = 0.031. The frequency of the XPD 312Asn allele was significantly higher in T ≥ 2 high grade than in T ≥ 2 low grade tumors (p = 0.036); the ERCC6 1097Val/Val genotype was strongly associated with muscle-invasive tumors. Combinations of homozygous wild type alleles occurred with the increased frequency in patients with non-muscle-invasive tumors suggesting that the maintenance of normal DNA repair activity may prevent cancer progression.

No MeSH data available.


Related in: MedlinePlus