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Distress and DNA repair in human lymphocytes 总被引:3,自引:0,他引:3
Janice K. Kiecolt-Glaser Ralph E. Stephens Philip D. Lipetz Carl E. Speicher Ronald Glaser 《Journal of behavioral medicine》1985,8(4):311-320
This research assessed differences in DNA repair in lymphocytes from high-and low-distressed individuals. A median split on Minnesota Multiphasic Personality Inventory (MMPI) Scale 2 divided 28 newly admitted nonpsychotic psychiatric inpatients into high- and low-distress subgroups. The high-distress subgroup had significantly poorer DNA repair in lymphocytes exposed to X-irradiation than low-distress subjects. We also found that lymphocytes obtained from this psychiatric sample had significantly poorer DNA repair than lymphocytes from nonpsychiatric control subjects when compared 5 hr after X-irradiation. A high level of distress therefore appears to be associated with significant dysfunctional differences at the molecular level which may have important implications for health. These data provide evidence for a direct pathway through which distress could influence the incidence of cancer.This research was funded in part by General Molecular Applications, Inc., the Bremer Foundation, the Samuel J. Roessler Fund, and Comprehensive Cancer Center Core Grant CA-16068-09. 相似文献
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顺铂的主要药理机制是损伤细胞DNA,肿瘤细胞DNA修复能力增强则会导致其对顺铂耐药。目前研究发现,DNA修复途径中的核苷酸切除修复、错配修复、碱基切除修复均与顺铂耐药有关,核苷酸切除修复为其中最为重要的途径。 相似文献
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DNA carries the genetic information that directs complex biological processes; thus, maintaining a stable genome is critical for individual growth and development and for human health. DNA repair is a fundamental and conserved mechanism responsible for mending damaged DNA and restoring genomic stability, while its deficiency is closely related to multiple human disorders. In recent years, remarkable progress has been made in the field of DNA repair and aging. Here, we will extensively discuss the relationship among DNA damage, DNA repair, aging and aging-associated diseases based on the latest research. In addition, the possible role of DNA repair in several potential rejuvenation strategies will be discussed. Finally, we will also review the emerging methods that may facilitate future research on DNA repair. 相似文献
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Summary The photoreactivation repair gene (PHR1) of the yeast Saccharomyces cerevisiae was cloned in a hybrid plasmid (pJDB207), which is able to replicate as a multicopy episome in S. cerevisiae and Escherichia coli cells. The size of the DNA fragment found to have the photoreactivation activity was 3.0 kb, determined by recloning of the isolated fragment. In wild type cells transformed by the plasmid containing the PHR1 gene, the number of DNA photolyase molecules was 15 times greater than in wild type cells with pJDB207 only. Using the same receptor strain the excision repair gen RAD1 was also isolated. The size of the insert of the DNA which complements excision repair deficiency in recipient yeast cells was 5.7 kb. The recipient cells after transformation with the plasmid containing RAD1 showed the same UV-sensitivty as wild type cells with pJDB207 only.Abbreviation UV
Ultra-violet light of 254 run wavelength 相似文献
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Alzheimer's disease (AD) has been correlated with elevated levels of oxidative DNA damage. Base excision repair (BER) is the main repair pathway for the removal of oxidative DNA base modifications. We have recently found significant functional deficiencies in BER in brains of sporadic AD and amnestic mild cognitive impairment patients. In this study we tested whether altered BER activities are associated with appearance of symptoms in different brain regions of pre-symptomatic and symptomatic mice harboring mutant APP alone or in combination with Tau and PS1. Our results suggest that unlike in humans, the development of AD-like pathology in the studied mouse models is not associated with deficiencies in BER. 相似文献
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Frailty is an emerging geriatric syndrome characterized by higher vulnerability to stressors, with an increased risk of adverse health outcomes such as mortality, morbidity, disability, hospitalization, and institutionalization. Although it is generally recognized to have a biological basis, no particular biological trait has been consistently associated to frailty status so far. In this work, epidemiological studies evaluating association of frailty status with alterations at cellular level − namely oxidative stress, genomic instability and DNA damage and repair biomarkers −were revised and compared. A total of 25 studies fulfilled inclusion/exclusion criteria and, consequently, were included in the review. Variations of oxidative stress biomarkers were often associated to frailty status in older people. On the contrary, genomic instability seems not to be linked to frailty. The only study which addressed the possible relationship between DNA repair modulations and frailty status also failed in finding association. Despite the large number of cellular alterations known to be associated with frailty, studies on this issue are still very scarce and limited to some of the possible cellular targets. The established link between DNA repair, genomic instability, and age and age-related disorders, encourage deeper investigations on this line. 相似文献
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Ricardo Gredilla Lior Weissman Jenq-Lin Yang Vilhelm A. Bohr Tinna Stevnsner 《Neurobiology of aging》2012
Brain aging is associated with synaptic decline and synaptic function is highly dependent on mitochondria. Increased levels of oxidative DNA base damage and accumulation of mitochondrial DNA (mtDNA) mutations or deletions lead to mitochondrial dysfunction, playing an important role in the aging process and the pathogenesis of several neurodegenerative diseases. Here we have investigated the repair of oxidative base damage, in synaptosomes of mouse brain during normal aging and in an AD model. During normal aging, a reduction in the base excision repair (BER) capacity was observed in the synaptosomal fraction, which was associated with a decrease in the level of BER proteins. However, we did not observe changes between the synaptosomal BER activities of presymptomatic and symptomatic AD mice harboring mutated amyolid precursor protein (APP), Tau, and presinilin-1 (PS1) (3xTgAD). Our findings suggest that the age-related reduction in BER capacity in the synaptosomal fraction might contribute to mitochondrial and synaptic dysfunction during aging. The development of AD-like pathology in the 3xTgAD mouse model was, however, not associated with deficiencies of the BER mechanisms in the synaptosomal fraction when the whole brain was analyzed. 相似文献
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In recent years, several novel congenital human disorders have been described with defects in lymphoid B‐cell and T‐cell functions that arise due to mutations in known and/or novel components of DNA repair and damage response pathways. Examples include impaired DNA double‐strand break repair, as well as compromised DNA damage‐induced signal transduction, including phosphorylation and ubiquitination. These disorders reinforce the importance of genome stability pathways in the development of lymphoid cells in humans. Furthermore, these conditions inform our knowledge of the biology of the mechanisms of genome stability and in some cases may provide potential routes to help exploit these pathways therapeutically. Here we review the mechanisms that repair programmed DNA lesions that occur during B‐cell and T‐cell development, as well as human diseases that arise through defects in these pathways. 相似文献
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XRCC1与DNA修复 总被引:3,自引:0,他引:3
蒋祝昌 《国际生物医学工程杂志》2003,26(5):234-237
XRCC1是影响细胞对电离辐射的敏感性的第一个哺乳类动物基因。XRCC1通过与PARP、DNA连接酶Ⅲ和DNA多聚酶β等作用,在DNA损伤时单链断裂修复中起重要作用。现就XRCC1的分子生物学特性及XRCC1在DNA修复可能机制进行综述。 相似文献
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L H Thompson 《Environmental and molecular mutagenesis》1989,14(4):264-281
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Nikolai M. Mironov Ghyslaine Martel-Planche Christopher P. Wild 《Environmental and molecular mutagenesis》1994,23(2):110-115
A procedure for measuring the level of O6-me-thylguanine (O6-meG) in DNA is described. Repair of 32P-oligodeoxynucleotides containing O6-meG adducts by O6-alkylguanine alkyltransferase (AGT) was performed in the presence of different quantities of DNA containing unknown concentrations of O6-meG. Each methylated DNA sample inhibited the repair of oli-godeoxynucleotide substrate to an extent dependent upon O6-meG concentration. Each DNA sample tested at different concentrations in the assay therefore had a characteristic inhibition curve and could be compared to the curves generated using reference DNA samples of known O6-meG concentration. We report the method of calculation of the O6-meG level in a given DNA sample by comparison of its inhibition curve with that of reference DNAs. This method of calculation does not require a knowledge of the exact quantity of the labelled substrate or AGT used. The method requires only 0.1-10 μg of DNA, with a limit of detection of 0.8 fmol of O6-meG per μg of DNA. © 1994 Wiley-Liss, Inc. 相似文献
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Mitochondrial DNA repair: a critical player in the response of cells of the CNS to genotoxic insults
Cells of the CNS are constantly exposed to agents which damage DNA. Although much attention has been paid to the effects of this damage on nuclear DNA, the nucleus is not the only organelle containing DNA. Within each cell, there are hundreds to thousands of mitochondria. Within each mitochondrion are multiple copies of the mitochondrial genome. These genomes are extremely vulnerable to insult and mutations in mitochondrial DNA (mtDNA) have been linked to several neurodegenerative diseases, as well as the normal process of aging. The principal mechanism utilized by cells to avoid DNA mutations is DNA repair. Multiple pathways of DNA repair have been elucidated for nuclear DNA. However, it appears that only base excision repair is functioning in mitochondria. This repair pathway is responsible for the removal of most endogenous damage including alkylation damage, depurination reactions and oxidative damage. Within the rat CNS, there are cell-specific differences mtDNA repair. Astrocytes exhibit efficient repair, whereas, other glial cell types and neuronal cells exhibit a reduced ability to remove lesions from mtDNA. Additionally, a correlation was observed between those cells with reduced mtDNA repair and an increase in the induction of apoptosis. To demonstrate a causative relationship, a strategy of targeting DNA repair proteins to mitochondria to enhance mtDNA repair capacity was employed. Enhancement of mtDNA repair in oligodendrocytes provided protection from reactive oxygen species- and cytokine-induced apoptosis. These experiments provide a novel strategy for protecting sensitive CNS cells from genotoxic insults and thus provide new treatment options for neurodegenerative diseases. 相似文献
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Fuli Zhao Yuhong Shang Chen Zeng Dongdong Gao Ke Li 《International journal of clinical and experimental pathology》2015,8(9):11579-11586
In our study, we conducted a case-control study to investigate the association of ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, XPA, XPC and DDB2 gene polymorphisms in the risk of pancreatic cancer. Between May 2012 and May 2014, a total of 246 patients with who were newly diagnosed with histopathologically confirmed primary pancreatic cancer and 246 controls were selected into our study. Genotyping of ERCC1 rs3212986 and rs11615, ERCC2 rs13181, ERCC3 rs4150441, ERCC4 rs6498486, ERCC5 rs873601, XPA rs2808668, XPC rs2228000, XPC rs2228001 and DDB2 rs2029298 were analyzed using polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). By conditional logistic regression analysis, individuals carrying with TT genotype of ERCC1 rs3212986 and GG genotype of ERCC2 rs13181 were associated with increased risk of pancreatic cancer when compared with wide-type genotype, and the adjusted ORs (95% CI) were 2.40 (1.29-4.52) and 2.27 (1.26-4.15), respectively. We found that individuals carrying with GT+TT genotype of ERCC1 rs3212986 and TG+GG genotype of ERCC2 rs1318 gene polymorphisms were correlated with higher risk of pancreatic cancer in smokers when compared with non-smokers, and the adjusted ORs (95% CI) were 1.89 (1.05-3.40) and 1.88 (1.06-3.34), respectively. In conclusion, our study suggests that ERCC1 rs3212986 and ERCC2 rs1318 gene polymorphisms contribute to the development of pancreatic cancer, especially in smokers. 相似文献
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M J Horsfall A J Gordon P A Burns M Zielenska G M van der Vliet B W Glickman 《Environmental and molecular mutagenesis》1990,15(2):107-122
Alkylating treatments predominantly induce G: C = greater than A:T transitions, consistent with the predicted significance of the miscoding potential of the O6-alG lesion. However, the frequency and distribution of these events induced by any one compound may be diagnostic. SN1 agents that act via an alkyldiazonium cation, such as the N-nitroso compounds, preferentially generate G: C = greater than A:T transitions at 5'-RG-3' sites, while the more SN2 alkylsulfates and alkylalkane-sulfonates do not. The precise nature of this site bias and the possibility of strand bias are target dependent. The extent of this site bias and the contribution of other base substitutions are substituent size dependent. A similar 5'-RT-3' effect is seen for A:T = greater than G:C transitions, presumably directed by O4-alT lesions. The 5'-RG-3' effect, at least, likely reflects a deposition specificity arising from some aspect of helix geometry, although it may be further exaggerated by alkylation-specific repair. Excision repair appears to preferentially reduce the occurrence of ethylation-induced G:C = greater than A:T and A:T = greater than G:C transitions at sites flanked by A:T base pairs. This may be due to an enhancement of the helical distortion imposed by damage at such positions. A similar effect is not seen for methylation-induced mutations and in the case of propyl adducts, the influence of excision repair on the ultimate distribution of mutation cannot be as easily defined with respect to neighbouring sequence. 相似文献