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61.
Imatinib (STI571) induces DNA damage in BCR/ABL-expressing leukemic cells but not in normal lymphocytes 总被引:2,自引:0,他引:2
Czechowska A Poplawski T Drzewoski J Blasiak J 《Chemico-biological interactions》2005,152(2-3):139-150
Imatinib (STI571) is a 2-phenylaminopyrimidine derivative used mostly in the treatment of chronic myeloid leukaemia. It targets the BCR/ABL oncogenic tyrosine kinase, inhibiting its activity. Using the alkaline comet assay we showed that STI571 at concentrations ranging from 0.2 to 2 microM induced DNA damage in human leukemic K562 and BV173 cells expressing the BCR/ABL oncogene, whereas it had no effect in normal human lymphocytes and leukemic CCRF-CEM cells without the expression of BCR/ABL. Imatinib did not induce DNA strand breaks in the direct interaction with DNA as examined by the circular plasmid relaxation assay. Because the extent of DNA damage observed in the neutral and pH 12.1 versions of the comet assay was much lesser than in the alkaline version, we concluded that the drug induced DNA alkali-labile sites rather than strand breaks. K562 cells were unable to repair H(2)O(2)-induced DNA damage during a 120-min incubation, if they had been preincubated with STI571, whereas normal lymphocytes did so within 60 min. Pre-treatment of K562 cells with Vitamins A, C and E reduced the extent of DNA damage evoked by STI571. Similar results brought experiments with the nitrone spin traps POBN and PBN, suggesting that free radicals may be involved in the formation of DNA lesions induced by STI571 in K562 cells. These cells exposed to imatinib and treated with endonuclease III, formamidopyrimidine-DNA glycosylase and 3-methyladenine-DNA glycosylase II, the enzymes recognizing oxidized and alkylated bases, displayed greater extent of DNA damage than those not treated with these enzymes. Therefore, the mechanism of the anti-leukemic action of STI571 may involve not only the inhibition of BCR/ABL, but also DNA damage in the cells expressing this fusion protein. DNA damage induced by STI571 may follow from oxidative and alkylative base modifications. 相似文献
62.
SE?Aleshin AV?Timofeev MV?Khoretonenko LG?Zakharova GV?Pashvykina JR?Stephenson AM?Shneider AD?AltsteinEmail author 《BMC microbiology》2005,5(1):45
Background
Heterologous prime-boost immunization protocols using different gene expression systems have proven to be successful tools in protecting against various diseases in experimental animal models. The main reason for using this approach is to exploit the ability of expression cassettes to prime or boost the immune system in different ways during vaccination procedures. The purpose of the project was to study the ability of recombinant vaccinia virus (VV) and bacterial plasmid, both carrying the NS1 gene from tick-borne encephalitis (TBE) virus under the control of different promoters, to protect mice against lethal challenge using a heterologous prime-boost vaccination protocol. 相似文献63.
Ustilago maydis, the causal agent of corn smut disease, displays dimorphic growth in which it alternates between a unicellular, nonpathogenic yeast-like form and a dikaryotic, pathogenic filamentous form. Previously, a constitutively filamentous haploid mutant was obtained. Complementation of this mutant led to the isolation of the gene encoding adenylate cyclase, uac1. Secondary mutagenesis of a uac1 disruption strain allowed the isolation of a large number of suppressor mutants, termed ubc, for Ustilago bypass of cyclase, lacking the filamentous phenotype. Analysis of one of these suppressor mutants previously led to the identification of the ubc1 gene, encoding the regulatory subunit of cAMP-dependent protein kinase. In this report we describe the isolation of cosmids containing three new ubc genes, termed ubc2, ubc3, and ubc4. We also describe the morphology of the ubc2, ubc3, and ubc4 mutants in a uac1- background as well as in a background with a functional uac1 gene. In addition, we describe several mutant strains not complemented with any of the genes currently in hand and that are thus presumed to possess mutations in additional ubc genes. Copyright 1998 Academic Press. 相似文献
64.
Variation in rates of molecular evolution now appears to be widespread. The
demonstration that body size is correlated with rates of molecular
evolution suggests that physiological and ecological factors may be
involved in molecular rate variation, but large-scale comparative studies
are still lacking. Here, we use complete cytochrome b sequences from 85
species of tube-nosed seabirds (order Procellariiformes) and 5 outgroup
species of penguins (order Sphenisciformes) to test for an association
between body mass and rates of molecular evolution within the former avian
order. Cladistic analysis of the 90 sequences estimates a phylogeny largely
consistent with the traditional taxonomy of the Procellariiformes. The
Diomedeidae, Procellariidae, and Pelecanoididae are monophyletic, while the
Hydrobatidae are basal and paraphyletic. However, the two subfamilies
within the Hydrobatidae (Hydrobatinae and Oceanitinae) are monophyletic. A
likelihood ratio test detects significant deviation from clocklike
evolution in our data. Using a sign test for an association between body
mass and branch length in the seabird phylogeny, we find that larger taxa
tend to have shorter terminal branch lengths than smaller taxa. This
observation suggests that rates of mitochondrial DNA evolution are slower
for larger taxa. Rate calibrations based on the fossil record reveal
concordant body size effects. We interpret these results as evidence for a
metabolic rate effect, as the species in this order exhibit large
differences in metabolic rates, which are known to be highly correlated
with body mass in this group. Our results support previous findings of body
size effects and show that this effect can be significant even within a
single avian order. This suggests that even lineage-specific molecular
clocks may not be tenable if calibrations involve taxa with different
metabolic rates.
相似文献
65.
66.
Molecular evolution of chloroplast DNA sequences 总被引:13,自引:1,他引:12
Comparative data on the evolution of chloroplast genes are reviewed. The
chloroplast genome has maintained a similar structural organization over
most plant taxa so far examined. Comparisons of nucleotide sequence
divergence among chloroplast genes reveals marked similarity across the
plant kingdom and beyond to the cyanobacteria (blue-green algae). Estimates
of rates of nucleotide substitution indicate a synonymous rate of 1.1 x
10(-9) substitutions per site per year. Noncoding regions also appear to be
constrained in their evolution, although addition/deletion events are
common. There have also been evolutionary changes in the distribution of
introns in chloroplast encoded genes. Relative to mammalian mitochondrial
DNA, the chloroplast genome evolves at a conservative rate.
相似文献
67.
We have performed a cell cycle analysis of organisms from the Archaea domain. Exponentially growing cells of the thermophilic archaea Sulfolobus solfataricus and Sulfolobus acidocaldarius were analyzed by flow cytometry, and several unusual cell cycle characteristics were found. The cells initiated chromosome replication shortly after cell division such that the proportion of cells with a single chromosome equivalent was low in the population. The postreplication period was found to be long; i.e., there was a considerable time interval from termination of chromosome replication until cell division. A further unusual feature was that cells in stationary phase contained two genome equivalents, showing that they entered the resting stage during the postreplication period. Also, a reduction in cellular light scatter was observed during entry into stationary phase, which appeared to reflect changes not only in cell size but also in morphology and/or composition. Finally, the in vivo organization of the chromosome DNA appeared to be different from that of eubacteria, as revealed by variation in the relative binding efficiency of different DNA stains. 相似文献
68.
People can eat a food without having a strong preference for it, and people can prefer a food without eating it. Given this seeming disconnect between attitude and behavior, which type of measure or segment can best be used to profile or identify loyal consumer segments of a food, such as soy? This research compares a usage‐based method (heavy‐light‐nonusers) with a new attitude‐based method (seeker‐neutral‐avoider), and finds that the attitude‐based method differentiates purchase‐related intentions better than the usage‐based method. Implications for profiling consumer taste patterns and consumer segments are provided. 相似文献
69.
A. Laperche Y. Aigu M. Jubault M. Ollier S. Guichard P. Glory SE. Strelkov A. Gravot MJ. Manzanares-Dauleux 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2017,130(4):669-684
Key message
Nitrogen levels can modulate the effectiveness of clubroot resistance in an isolate- and host-specific manner. While the same QTL were detected under high and low nitrogen, their effects were altered.Abstract
Clubroot, caused by Plasmodiophora brassicae, is one of the most damaging diseases of oilseed rape and is known to be affected by nitrogen fertilization. However, the genetic factors involved in clubroot resistance have not been characterized under nitrogen-limiting conditions. This study aimed to assess the variability of clubroot resistance under different nitrogen levels and to characterize the impact of nitrogen supply on genetic resistance factors. Linkage analyses and a genome-wide association study were conducted to detect QTL for clubroot resistance and evaluate their sensitivity to nitrogen. The clubroot response of a set of 92 diverse oilseed rape accessions and 108 lines derived from a cross between ‘Darmor-bzh’ (resistant) and ‘Yudal’ (susceptible) was studied in the greenhouse under high- and low-nitrogen conditions, following inoculation with the P. brassicae isolates eH and K92-16. Resistance to each isolate was controlled by a major QTL and a few small-effects QTL. While the same QTL were detected under both high and low nitrogen, their effects were altered. Clubroot resistance to isolate eH, but not K92-16, was greater under a low-N supply versus a high-N supply. New sources of resistance were found among the oilseed rape accessions under both low and high-N conditions. The results are discussed relative to the literature and from a crop improvement perspective.70.
MARIA-MARCELA POVEDA MARIE-CLAUDE SOUQUAL MARIE-THÉRÈSE FAUVEL JACQUES GAMISANS THIERRY GAUQUELIN 《Botanical journal of the Linnean Society. Linnean Society of London》2002,140(2):165-168
The cuticular wax composition of leaves has been analysed in three western European populations (Corsica, central Pyrenees, northern Alps) of Juniperus communis var. saxatilis Pall. (= J. nana Willd., nom illeg.) and in one population of J. communis L. var. depressa Pursh. from North America (Sierra Nevada). Gas chromatography shows the presence of 13 alkanes in all samples ranging from C23 to C35 with important intraspecific polymorphism in alkane content. The dominant alkanes range from C33 to C35 . Alkanes C21 and C22 were found only in Corsica and Sierra Nevada populations. Canonical discriminant analysis separated the J. communis L. var. depressa Pursh. of the population of Sierra Nevada from other populations of J. communis var. saxatilis Pall. on the basis of their higher C31 content and the constant presence of C21 and C22 alkanes. J. communis var. saxatilis Pall. populations from the Pyrenees are close to northern Alps populations characterized by high concentrations of C33 , C34 and C35 alkanes. This paper confirms the existence of Juniperus var. saxatilis Pall. in the Pyrenees (France). © The Linnean Society of London, Botanical Journal of the Linnean Society , 2002, 140 , 165–168. 相似文献