Mutation Research/DNAging最新文献_第10页

Telomere loss: mitotic clock or genetic time bomb? 端粒丢失:有丝分裂时钟还是基因定时炸弹?

Mutation Research/DNAging Pub Date : 1991-03-01 DOI: 10.1016/0921-8734(91)90018-7

Calvin B. Harley

{"title":"Telomere loss: mitotic clock or genetic time bomb?","authors":"Calvin B. Harley","doi":"10.1016/0921-8734(91)90018-7","DOIUrl":"10.1016/0921-8734(91)90018-7","url":null,"abstract":"<div><p>The Holy Grail of gerontologists investigating cellular senescence is the mechanism responsible for the finite proliferative capacity of somatic cells. In 1973, Olovnikov proposed that cells lose a small amount of DNA following each round of replication due to the inability of DNA polymerase to fully replicate chromosome ends (telomeres) and that eventually a critical deletion causes cell death. Recent observations showing that telomeres of human somatic cells act as a mitotic clock, shortening with age both in vitro and in vivo in a replication dependent manne, support this theory's premise. In addition, since telomeres stabilize chromosome ends against recombination, their loss could explain the increased frequency of dicentric chromosomes observed in late passage (senescent) fibroblasts and provide a checkpoint for regulated cell cycle exit. Sperm telomeres are longer than somatic telomeres and are maintained with age, suggesting that germ line cells may express telomerase, the ribonucleoprotein enzyme known to maintain telomere length in immortal unicellar eukaryotes. As predicted, telomerase activity has been found in immortal, transformed human cells and tumour cell lines, but not in normal somatic cells. Telomerase activation may be a late, obligate event in immortalization since many transformed cells and tumour tissues have critically short telomeres. Thus, telomere length and telomerase activity appear to be markers of the replicative history and proliferative potential of cells; the intriguing possibility remains that telomere loss is a genetic time bomb and hence causally involved in cell senescence and immortalization.</p></div>","PeriodicalId":100937,"journal":{"name":"Mutation Research/DNAging","volume":"256 2","pages":"Pages 271-282"},"PeriodicalIF":0.0,"publicationDate":"1991-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0921-8734(91)90018-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12885629","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1183

Ageing in the chick lens: in vitro studies 小鸡晶状体的衰老:体外研究

Mutation Research/DNAging Pub Date : 1991-03-01 DOI: 10.1016/0921-8734(91)90012-Z

R.M. Clayton , C.E. Patek , M.W. Head , J. Cuthbert

{"title":"Ageing in the chick lens: in vitro studies","authors":"R.M. Clayton , C.E. Patek , M.W. Head , J. Cuthbert","doi":"10.1016/0921-8734(91)90012-Z","DOIUrl":"10.1016/0921-8734(91)90012-Z","url":null,"abstract":"<div><p>In principle, ageing may be due to the interaction of several factors, including the accumulation of random changes both genomic and non-genomic, secondary changes in a tissue contingent upon the changing function of other tissues, and programmed non-random changes in the tissue-specific expression of various genes.</p><p>The use of a single tissue comprising one cell type only, in which the major gene products are well defined, in which there is a well attested series of developmental and age-related changes in cell properties and gene expression and which can be studied and compared in vivo and in vitro, offers advantages for investigation of these questions. The vertebrate eye lens possesses these advantages. The crystallins (proteins expressed at super-abundant levels in the lens) are well characterised. The lens epithelial cells (LEC) grow readily and can differentiate into the lens fibre cells in vitrom, and, finally, such terminally differentiated cells may also be derived, by a process of transdifferentiation, from neural retina cells (NRC) in vitro. Thus the effect on ageing changes of the tissue of origin may also be studied. This article reviews our previous studies on long-term changes in growth potential, differentiation capacity and crystallin expression of chick lens cells in ageing cultures, their overall similarity to events in vivo and the effect on ageing changes of genotypes affecting the growth rate. It presents new information on these genetic aspects, and on crystallin expression in long-term ageing cultures of transdifferentiated neural retina, and compares the behaviour of ageing chick lens cells with that reported for mammals.</p></div>","PeriodicalId":100937,"journal":{"name":"Mutation Research/DNAging","volume":"256 2","pages":"Pages 203-220"},"PeriodicalIF":0.0,"publicationDate":"1991-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0921-8734(91)90012-Z","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12885670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 6

Involvement of microtubules in modifications associated with cellular aging 微管参与与细胞衰老相关的修饰

Mutation Research/DNAging Pub Date : 1991-03-01 DOI: 10.1016/0921-8734(91)90008-Y

Martine Raes

{"title":"Involvement of microtubules in modifications associated with cellular aging","authors":"Martine Raes","doi":"10.1016/0921-8734(91)90008-Y","DOIUrl":"10.1016/0921-8734(91)90008-Y","url":null,"abstract":"<div><p>Microtubules are ubiquitous cellular components involved in the control of cell structure and functions, such as cell division, regulation of shape and polarity, intracellular transport, etc. Consequently, any alteration affecting them in structure or function has a good chance of affecting the cell and generally leads to cell dysfunctions. This has been shown for instance, after treatment with microtubule- interacting drugs. Cellular aging is also characterized by the appearance of various cell dysfunctions, but the possible involvement of the microtubules in the aging process, although a rather tempting hypothesis, has not yet been extensively investigated.</p><p>In this paper, I will first rapidly review the different components that build, organize and control the microtubules in normal cells, independently of the aging process. I will then consider the possible involvement of the microtubules in the aging process, more particularly in models of cells aging in vitro and in aging neuronal cells, which have been the most extensively investigated. There is some evidence for alterations in the microtubule organization both in cells aging in vitro and in the aging brain. But the interpretation of these data awaits further experiments, taking into account the latest progress in tubulin genetics and in microtubule biochemistry.</p><p>Microtubules could also represent one of the cellular targets affected after signal transduction and could thus be involved in the resulting cellular responses. This hypothesis will be discussed, as it offers new insights into the regulation of microtubule organization, dynamics and functions in normal cells, which will be worthwhile to investigate during the aging process.</p></div>","PeriodicalId":100937,"journal":{"name":"Mutation Research/DNAging","volume":"256 2","pages":"Pages 149-168"},"PeriodicalIF":0.0,"publicationDate":"1991-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0921-8734(91)90008-Y","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12886358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

The formation of heart DNA adducts in F344 rats following dietary administration of heterocyclic amines 杂环胺对F344大鼠心脏DNA加合物形成的影响

Mutation Research/DNAging Pub Date : 1991-01-01 DOI: 10.1016/0921-8734(91)90031-6

Eva Övervik, Masako Ochiai, Misako Hirose, Takashi Sugimura, Minako Nagao

{"title":"The formation of heart DNA adducts in F344 rats following dietary administration of heterocyclic amines","authors":"Eva Övervik, Masako Ochiai, Misako Hirose, Takashi Sugimura, Minako Nagao","doi":"10.1016/0921-8734(91)90031-6","DOIUrl":"10.1016/0921-8734(91)90031-6","url":null,"abstract":"<div><p>Most heterocyclic amines formed during the cooking of meat and fish have been shown to form adducts in the livers of rats. Recently, however, 2-amino-1-methyl-6-phenylimidazo{4,5-<em>b</em>}pyridine (PhIP), administered in the diet to Fischer 344 (F344) rats for 4 weeks, was shown to produce the highest levels of adducts in the heart. In the present study 2-amino-3-methylimidazo–[4,5<em>f</em>–]quinoline (IQ), 2-amino-3,8-dimethylimidazo{4,5-<em>f</em>}quinoxaline (MeIQx), 3-amino-1,4-dimethyl-5<em>H</em>-pyrido{4,3-<em>b</em>}indole (Trp-P-1) and 2-amino-6-methyldipyrido{1,2-<em>a</em>:1′,2′-<em>d</em>}imidazole (Glu-P-1) were given to F344 rats at carcinogenic dose levels (IQ 0.03%, MeIQx 0.04%, Trp-P-1 0.015%, Glu-P-1 0.05%) in the diet for 4 weeks. DNA adducts in the liver and heart were analyzed by <sup>32</sup>P-postlabeling. DNA adducts were demonstrated to appear in the hearts of all animals exposed to heterocyclic amines at the following levels: IQ, 1.8 adducts/10<sup>7</sup> nucleotides, MeIQx, <span><math><mtext>3.8</mtext><mtext>10</mtext><msup><mi></mi><mn>7</mn></msup></math></span> ntd, Trp-P-1, <span><math><mtext>20</mtext><mtext>10</mtext><msup><mi></mi><mn>7</mn></msup></math></span> ntd and Glu-P-1, <span><math><mtext>7.2</mtext><mtext>10</mtext><msup><mi></mi><mn>7</mn></msup></math></span> ntd. Values for the heart were 10–20% of the respective liver adduct levels. Heart adducts increased linearly throughout the observed period when MeIQx was administered for up to 40 weeks. When MeIQx feeding was discontinued after 20 weeks and the animals subsequently given the basal diet, the adduct level at 20 weeks did not change during the following 20 weeks. A possible role for heart DNA alterations caused by food-borne heterocyclic amines in the development of age-related myopathies and cardiovascular disease is not inconceivable.</p></div>","PeriodicalId":100937,"journal":{"name":"Mutation Research/DNAging","volume":"256 1","pages":"Pages 37-43"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0921-8734(91)90031-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13103995","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 20

Heterogeneity in Alzheimer's disease: evidence from cellular radiosensitivity and complementation of this phenotype 阿尔茨海默病的异质性:来自细胞放射敏感性和该表型互补的证据

Mutation Research/DNAging Pub Date : 1991-01-01 DOI: 10.1016/0921-8734(91)90029-B

Philip Chen, Chev Kidson , Martin Lavin

引用次数: 6

Micronucleated lymphocytes in people occupationally exposed to potential environmental contaminants: the age effect 职业暴露于潜在环境污染物人群的微核淋巴细胞:年龄效应

Mutation Research/DNAging Pub Date : 1991-01-01 DOI: 10.1016/0921-8734(91)90028-A

L. Migliore , M. Parrini , I. Sbrana , C. Biagini , A. Battaglia , N. Loprieno

{"title":"Micronucleated lymphocytes in people occupationally exposed to potential environmental contaminants: the age effect","authors":"L. Migliore , M. Parrini , I. Sbrana , C. Biagini , A. Battaglia , N. Loprieno","doi":"10.1016/0921-8734(91)90028-A","DOIUrl":"10.1016/0921-8734(91)90028-A","url":null,"abstract":"<div><p>This work is part of a research project on 2 groups of tannery workers (i.e., workers employed in the tanning process and those employed in the finishing department), and 2 control groups consisting of individuals paired with each exposed person according to sex, age and smoking habit. The whole study included the evaluation of micronuclei as well as of chromosomal aberrations and sister-chromatid exchanges in peripheral blood lymphocytes. Data on micronucleus analysis in both controls and exposed persons are shown in this paper. There was no statistically significant difference between MN frequencies in the 2 groups of exposed and controls, nor any positive correlation with smoking habit. The effect of age on basal frequency of micronucleated cells clearly emerges in the present study: both controls and exposed show an increase in MN frequency due to age. This could be correlated with a higher sensitivity to breaks, rearrangements or aneuploidogenic events of circulating lymphocytes in aged people.</p></div>","PeriodicalId":100937,"journal":{"name":"Mutation Research/DNAging","volume":"256 1","pages":"Pages 13-20"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0921-8734(91)90028-A","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13103993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 115

Biochemical mechanisms by which reutilization of DNA 5-methylcytosine is prevented in human cells 阻止人体细胞中DNA 5-甲基胞嘧啶再利用的生化机制

Mutation Research/DNAging Pub Date : 1991-01-01 DOI: 10.1016/0921-8734(91)90030-F

Juhani A. Vilpo, Leena A. Vilpo

{"title":"Biochemical mechanisms by which reutilization of DNA 5-methylcytosine is prevented in human cells","authors":"Juhani A. Vilpo, Leena A. Vilpo","doi":"10.1016/0921-8734(91)90030-F","DOIUrl":"10.1016/0921-8734(91)90030-F","url":null,"abstract":"<div><p>The salvage metabolism of 5-methyldeoxycytidine 5′-monophosphate (5MedCMP) was studied in human promyelocytic leukemia (HL-60) cells and in PHA-stimulated human lymphocytes. To this end [5′-<sup>32</sup>P]5MedCMP was synthesized by a novel postlabeling procedure. At low substrate concentrations (< 100 <em>μ</em>M), the enzyme(s) present in crude HL-60 whole-cell extract deaminated 5MedCMP faster than they did dCMP. Although the phosphorylation of dCMP to dCDP was easily demonstrable with both kinds of cell extracts, no phosphorylation of 5MedCMP to 5MedCDP (5-methyldeoxycytidine 5′-diphosphate) was observed. This phenomenon was confirmed using HL-60 cells made permeable to nucleotides with Tween 80. In view of the substantial 5MeCyt (5-methylcytosine) content of DNA and the degradation of DNA that occurs in cells, it is conceivable that 5MedCyd (5-methyl-2′-deoxycytidine) and 5MedCMP are available for reutilization in DNA synthesis. This would have devastating effects on cellular control and gene expression. The results of the present investigation indicate that rapid deamination at the monophosphate level and, in particular, stringent discrimination of 5MedCMP by cellular monophosphokinase(s) are the key mechanisms by which reutilization of DNA 5MeCyt is prevented in human hematopoietic cells.</p></div>","PeriodicalId":100937,"journal":{"name":"Mutation Research/DNAging","volume":"256 1","pages":"Pages 29-35"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0921-8734(91)90030-F","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"12883151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 12

The effects of spermatozoal irradiation with X-rays on chromosome abnormalities and on development of mouse zygotes after delayed fertilization 精子x射线照射对小鼠延迟受精后染色体异常和受精卵发育的影响

Mutation Research/DNAging Pub Date : 1991-01-01 DOI: 10.1016/0921-8734(91)90033-8

M.L. Boerjan, L.A. Saris

{"title":"The effects of spermatozoal irradiation with X-rays on chromosome abnormalities and on development of mouse zygotes after delayed fertilization","authors":"M.L. Boerjan, L.A. Saris","doi":"10.1016/0921-8734(91)90033-8","DOIUrl":"10.1016/0921-8734(91)90033-8","url":null,"abstract":"<div><p>The chromosome complements of zygotes derived from oocytes aged post ovulation and fertilized in vivo with X-ray-irradiated sperm were studied. Ovulation was induced by an injection of luteinizing hormone-releasing hormone (LHRH) at pro-estrus and fertilization was achieved by artificial insemination at 13 h and 24 h after LHRH in order to obtain embryos from unaged and aged (12 h post-ovulation) oocytes respectively. Post-ovulatory aging prior to fertilization did not significantly affect the percentage of zygotes with irradiation-induced chromosome abnormalities. However, post-ovulatory aging had a negative effect on the morphology of male as well as female pronuclear chromosomes of the first cleavage metaphase. When fertilized with control spermatozoa this effect was apparent in both the male and the female pronucleus. When unaged oocytes were fertilized with X-irradiated spermatozoa chromosome morphology was also adversely affected in both pronuclei. In zygotes from aged oocytes, there was an extra negative effect of X-rays on the male pronuclear chromosomes only.</p><p>After fertilization with X-irradiated sperm 27% of zygotes from aged oocytes were arrested at interphase compared to 7% from unaged oocytes.</p><p>We suggest that post-ovulatory aging and X-rays affect the male and female pronuclear chromatin structure after fertilization. These chromatin alterations could interact with DNA lesions induced in the spermatozoa prior to fertilization, such that development to first cleavage can be blocked.</p></div>","PeriodicalId":100937,"journal":{"name":"Mutation Research/DNAging","volume":"256 1","pages":"Pages 49-57"},"PeriodicalIF":0.0,"publicationDate":"1991-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0921-8734(91)90033-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13103997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7

Extrachromosomal circular DNAs and genomic sequence plasticity in eukaryotic cells 真核细胞染色体外环状dna和基因组序列可塑性

Mutation Research/DNAging Pub Date : 1990-09-01 DOI: 10.1016/0921-8734(90)90009-G

James W. Gaubatz

引用次数: 153

Proliferation-dependent regulation of DNA glycosylases in progeroid cells DNA糖基酶在类早衰细胞中的增殖依赖性调控

Mutation Research/DNAging Pub Date : 1990-09-01 DOI: 10.1016/0921-8734(90)90002-9

Barbara L. Cool , Michael A. Sirover

{"title":"Proliferation-dependent regulation of DNA glycosylases in progeroid cells","authors":"Barbara L. Cool , Michael A. Sirover","doi":"10.1016/0921-8734(90)90002-9","DOIUrl":"10.1016/0921-8734(90)90002-9","url":null,"abstract":"<div><p>The regulation of the base excision repair enzymes uracil DNA glycosylase and hypoxanthine DNA glycosylase was examined in 2 different progeroid cell strains. The immunoreactivity of the uracil DNA glycosylase in progeroid cells was examined by enzyme linked immunosorbent assay (ELISA) and by immunoblot analysis. The enzyme was recognized in a quantitative manner by 2 different anti-human uracil DNA glycosylase monoclonal antibodies in the ELISA. Western blot analysis identified a glycosylase protein of <em>M</em><sub>r</sub> = 37,000. In randomly proliferating progeroid cells, the uracil DNA glycosylase was enhanced 3-fold during cell growth. In synchronous cells, uracil DNA glycosylase and hypoxanthine DNA glycosylase were induced with an extent of induction (5–6-fold) comparable to that observed for normal human cells. Further, the activity of each base excision repair enzyme was enhanced with a comparable temporal sequence prior to the induction of DNA synthesis and DNA polymerase activity. These results indicate a normal cell cycle regulation of base excision repair in progeroid cells.</p></div>","PeriodicalId":100937,"journal":{"name":"Mutation Research/DNAging","volume":"237 5","pages":"Pages 211-220"},"PeriodicalIF":0.0,"publicationDate":"1990-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0921-8734(90)90002-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"13235078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 7