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排序方式: 共有297条查询结果,搜索用时 15 毫秒
61.
62.
N M King G G Oakley M Medvedovic K Dixon 《Environmental and molecular mutagenesis》2001,37(4):329-339
Studies of ultraviolet (UV) light mutagenesis have demonstrated mutations at common sites in the target genes of shuttle vector plasmids replicated in cultured cells or by cellular extracts. The reasons for the specific pattern of mutagenesis are largely unknown. We have examined the specificity of UV-induced mutagenesis by replicating plasmid pLS189, irradiated with 40 J/m(2) UVC or unirradiated, in either xeroderma pigmentosum group A (XP-A) or HeLa cellular extracts. The XP-A extract displayed slightly lower replication ability, but produced a higher mutant frequency, compared to that of HeLa extract. Use of irradiated plasmid inhibited replication by an average of 63% and increased the mutant frequency by an average of 16.7-fold. Analysis of mutation spectra revealed nonrandom patterns of mutagenesis that differed significantly between HeLa and XP-A extracts. In comparison to HeLa extract, replication in XP-A extract resulted in lower frequencies of GC --> AT transitions and tandem double-base substitutions, and a higher frequency of deletions. Replication in HeLa extract produced hotspots at positions 100, 108, and 156 that were not produced by XP-A extract. Furthermore, XP-A extract produced hotspots at positions 124, 133, and 164, sites not characteristic of previous UV-induced mutagenesis studies using XPA-expressing cells. Addition of purified XPA protein to reactions containing XP-A extract altered each of these parameters, including loss of the hotspots at positions 124 and 133, to yield a more HeLa-like spectrum. These results indicate a previously uncharacterized role of the XPA protein in influencing the specificity of UV-induced mutagenesis during DNA replication. 相似文献
63.
The age-related expression decline of ERCC1 and XPF for forensic age estimation: A preliminary study
The age-related capacity decline of DNA damage repair in human peripheral blood has been demonstrated. Excision repair cross-complementation group1 (ERCC1) and Xeroderma pigmentosum complementation group F (XPF) were rate-limiting enzyme in nucleotide excision repair (NER) which was known as the most important DNA damage repair system. Consequently, we hypothesized that the expression and/or activity of ERCC1 and XPF may be associated with age. However, little was known about the quantitative relationship of ERCC1 and XPF expression levels with age. The aim of the present study was to analyze the correlation of ERCC1 and XPF expression levels with age by detecting the ERCC1 and XPF mRNA levels in peripheral blood mononuclear cells(PBMCs) and protein levels in plasma in healthy ethnic Han Chinese individuals, and finally find new molecular markers for forensic age estimation by establishing the mathematical model between ERCC1 and XPF expression levels and age. The results showed that the ERCC1 and XPF mRNA relative expression levels in PBMCs declined in an age-dependent manner (r = −0.578/−0.844, respectively, P < 0.01). The formula for age estimation based on the ERCC1 and XPF mRNA relative expression levels decline in PBMCs were Y = 3.3E−5x2−0.0261x+1.9175 (R2 = 0.3244, P < 0.01) and Y = 0.0003x2−0.0459x+2.0439 (R2 = 0.729, P < 0.01), respectively. There were no significant differences of the ERCC1 or XPF protein expression levels in plasma between age groups (P > 0.05). Furthermore, there were no significant differences of the ERCC1 or XPF mRNA and/or protein expression levels between males and females(P > 0.05). It suggested that the ERCC1 and XPF mRNA expression levels could be considered as valuable additional tool in individual age estimation, especially in cases where traditional morphologic method was inefficient or absent in forensic practice. 相似文献
64.
Guo W Zhou RM Wan LL Wang N Li Y Zhang XJ Dong XJ 《Journal of cancer research and clinical oncology》2008,134(2):263-270
Aim Inherited polymorphisms of DNA repair genes may contribute to variations in DNA repair capacity (DRC) and genetic susceptibility
to different cancers. The aim of this study was to determine whether single nucleotide polymorphisms (SNPs) of xeroderma pigmentosum
group A (XPA) and XPC can influence the risk of esophageal squamous cell carcinoma (ESCC).
Methods In this report, one SNP of XPA and three SNPs of XPC were genotyped by polymerase-chain reaction (PCR) and PCR-restriction
fragment length polymorphism (PCR-RFLP) assay in 327 ESCC patients and 612 healthy controls in a high incidence region of
North China.
Results Family history of upper gastrointestinal cancers (UGIC) may increase the risk of developing ESCC. The overall genotype and
allelotype distributions of XPA A23G in ESCC patients were significantly different from that in healthy controls (P < 0.05). The A/G + G/G genotype significantly decreased the risk of developing ESCC compared with A/A genotype. When stratified
for family history of UGIC, compared with A/A genotype, A/G + G/G genotype significantly decreased the risk of ESCC in groups
with negative history of UGIC. The overall genotype and allelotype distributions of XPC intron 9 PAT+/- and exon 15 Lys939Gln and exon 8 Val499Ala in ESCC patients were not significantly different from that in healthy controls
(P > 0.05). When stratified for smoking status and UGIC family history, compared with A/A genotype, C/C genotype of exon 15
Lys939Gln significantly increased the risk of developing ESCC in non-smoker group.
Conclusions We concluded that XPA23 polymorphism may be useful markers for identifying individuals at risk of developing ESCC. C/C genotype
of XPC exon 15 may be one of the factors that affect the risk of developing ESCC in nonsmoking population in the high incidence
region of China. 相似文献
65.
Monika Hanova Rudolf Stetina Radka Vaclavikova Zdenek Smerhovsky Alessio Naccarati Pavel Soucek Paola Manini Kari Hemminki 《Toxicology and applied pharmacology》2010,248(3):194-200
Decreased levels of single-strand breaks in DNA (SSBs), reflecting DNA damage, have previously been observed with increased styrene exposure in contrast to a dose-dependent increase in the base-excision repair capacity. To clarify further the above aspects, we have investigated the associations between SSBs, micronuclei, DNA repair capacity and mRNA expression in XRCC1, hOGG1 and XPC genes on 71 styrene-exposed and 51 control individuals. Styrene concentrations at workplace and in blood characterized occupational exposure. The workers were divided into low (below 50 mg/m3) and high (above 50 mg/m3) styrene exposure groups. DNA damage and DNA repair capacity were analyzed in peripheral blood lymphocytes by Comet assay. The mRNA expression levels were determined by qPCR. A significant negative correlation was observed between SSBs and styrene concentration at workplace (R = − 0.38, p = 0.001); SSBs were also significantly higher in men (p = 0.001). The capacity to repair irradiation-induced DNA damage was the highest in the low exposure group (1.34 ± 1.00 SSB/109 Da), followed by high exposure group (0.72 ± 0.81 SSB/109 Da) and controls (0.65 ± 0.82 SSB/109 Da). The mRNA expression levels of XRCC1, hOGG1 and XPC negatively correlated with styrene concentrations in blood and at workplace (p < 0.001) and positively with SSBs (p < 0.001). Micronuclei were not affected by styrene exposure, but were higher in older persons and in women (p < 0.001). In this study, we did not confirm previous findings on an increased DNA repair response to styrene-induced genotoxicity. However, negative correlations of SSBs and mRNA expression levels of XRCC1, hOGG1 and XPC with styrene exposure warrant further highly-targeted study. 相似文献
66.
67.
Mark Berneburg 《Journal der Deutschen Dermatologischen Gesellschaft》2010,8(10):776-778
Mitochondria, responsible for the generation of energy in our cells, contain their own genome, mitochondrial (mt)DNA. It is known that mutations of mtDNA accumulate during normal aging and that this can be accelerated by oxidative stress, i.e. induced by ultraviolet radiation. These mutations are functionally relevant and they play a causative role in normal aging as well as premature aging induced by ultraviolet radiation. While the focus of scientific research was more on epidermis and dermis within the last years, alterations of subcutaneous fat tissue were not investigated thus far. Cockayne syndrome (CS) A and B are two proteins known to repair oxidatively induced DNA damage via nucleotide excision repair (NER) in the nucleus. We could show that these two proteins enrich in mitochondria upon oxidative stress, directly interact with mtDNA and the two repair‐associated proteins mtSSBP‐1 and mtOGG‐1 and protect from deletions of mtDNA. If CSA or CSB are lacking, mtDNA mutations accumulate particularly in the cells of subcutaneous fat tissue which appears to mediate loss of adipocytes via apoptosis. Therefore, the two NER‐associated proteins CSA and CSB appear to play a direct role in protection from mutations which in turn are causative in aging‐associated loss of subcutaneous fat tissue. 相似文献
68.
Jorgensen TJ Visvanathan K Ruczinski I Thuita L Hoffman S Helzlsouer KJ 《Breast cancer research and treatment》2007,101(1):65-71
Background The genes mutated in the cancer-prone syndrome, xeroderma pigmentosum (XP genes), have been well studied both biochemically
and mechanistically. These genes are important components of the DNA nucleotide excision repair (NER) pathway, which protects
against environmentally-induced cancers. XP genes are also downstream of the hereditary breast cancer syndrome gene, BRCA1,
suggesting that XP genes may be important to hereditary forms of breast cancer as well. Although mutated XP genes are rare,
polymorphic forms with potential functional deficiencies are common, and could pose a significant cancer risk in the general
population.
Hypothesis This study tested the hypothesis that common polymorphic variants of XP genes were associated with the risk of breast cancer
among a population of women in Washington County, Maryland.
Methods Five single nucleotide polymorphisms (SNPs) among four XP genes (XPC, XPD, XPF and XPG) were genotyped from DNA samples collected
at baseline, and then analyzed by conditional logistic regression for association with the incidence of breast cancer. 321
cases were individually matched to 321 controls, by age and menopausal status.
Results No significant associations were found between breast cancer risk and any of the XP genotypes. Odds ratios for all genotypes
ranged from 0.61 to 1.14, and none were statistically significant. Adjustment and stratification for family history of breast
cancer did not alter the findings.
Conclusion These results suggest that polymorphisms of XP genes are not likely to be significant risk factors for women within the general
population. This study did not address, however, risks for subpopulations of women with high exposures to DNA damaging agents. 相似文献
69.
70.
Xeroderma pigmentosum group D 751 polymorphism as a predictive factor in resected gastric cancer treated with chemo-radiotherapy 总被引:5,自引:0,他引:5
Zárate RN Arias F Bandres E Cubedo E Malumbres R García-Foncillas J 《World journal of gastroenterology : WJG》2006,12(37):6032-6036
INTRODUCTION The xeroderma pigmentosum group D (XPD) gene en- codes a protein required for nucleotide excision repair (NER). This product recognizes and repairs a wide range of structurally unrelated lesions such as bulky adducts caused by UV light, envir… 相似文献