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排序方式: 共有86条查询结果,搜索用时 15 毫秒
1.
The alkaline elution of bromodeoxyuridine-containing (BrdUrd) DNA and chlorodeoxyuridine-containing ( CldUrd ) DNA was studied in two CHO lines, the parental AA8 and a mutant line, EM9 , which has a defect in repairing strand breaks and a 12-fold elevated baseline frequency of SCE. BrdUrd-DNA was found to have alkali-labile sites as well as direct breaks, neither of which were increased significantly by prior treatment of AA8 cells with an inhibitor (benzamide) or poly(adenosine diphosphoribose) polymerase. CldUrd -DNA, which gives higher frequencies of SCEs than BrdUrd-DNA, had more strand breaks than BrdUrd-DNA in AA8 cells after treatment with benzamide, while without benzamide there was no difference. The accumulation of breaks in CldUrd -DNA by benzamide was shown to occur rapidly, to reach a maximum by 90 min, and to be readily reversible after benzamide removal. Under all conditions, EM9 cells had more strand breaks than AA8 . These observed differences in strand breaks were not due to differences in incorporation efficiencies. For the different halogenated pyrimidines and cell types, there was a good correlation between the number of strand breaks and reduction in plating efficiencies. 相似文献
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V KW Wong T Li B YK Law E DL Ma N C Yip F Michelangeli C KM Law M M Zhang K YC Lam P L Chan L Liu 《Cell death & disease》2013,4(7):e720
Autophagy is an important cellular process that controls cells in a normal homeostatic state by recycling nutrients to maintain cellular energy levels for cell survival via the turnover of proteins and damaged organelles. However, persistent activation of autophagy can lead to excessive depletion of cellular organelles and essential proteins, leading to caspase-independent autophagic cell death. As such, inducing cell death through this autophagic mechanism could be an alternative approach to the treatment of cancers. Recently, we have identified a novel autophagic inducer, saikosaponin-d (Ssd), from a medicinal plant that induces autophagy in various types of cancer cells through the formation of autophagosomes as measured by GFP-LC3 puncta formation. By computational virtual docking analysis, biochemical assays and advanced live-cell imaging techniques, Ssd was shown to increase cytosolic calcium level via direct inhibition of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump, leading to autophagy induction through the activation of the Ca2+/calmodulin-dependent kinase kinase–AMP-activated protein kinase–mammalian target of rapamycin pathway. In addition, Ssd treatment causes the disruption of calcium homeostasis, which induces endoplasmic reticulum stress as well as the unfolded protein responses pathway. Ssd also proved to be a potent cytotoxic agent in apoptosis-defective or apoptosis-resistant mouse embryonic fibroblast cells, which either lack caspases 3, 7 or 8 or had the Bax-Bak double knockout. These results provide a detailed understanding of the mechanism of action of Ssd, as a novel autophagic inducer, which has the potential of being developed into an anti-cancer agent for targeting apoptosis-resistant cancer cells. 相似文献
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5.
Lemonnier LA Dillehay DL Vespremi MJ Abrams J Brody E Schmelz EM 《Archives of biochemistry and biophysics》2003,419(2):129-138
Intestinal cells are regularly exposed to sphingolipid metabolites, i.e., ceramide and sphingoid bases, after hydrolysis of complex sphingolipids from the diet. These metabolites are known regulators of cell growth, differentiation, and death. Non-pharmacological amounts in the diet have been shown to inhibit early stages of chemically induced colon cancer in mice. To distinguish between chemopreventive and chemotherapeutic effects of sphingomyelin supplements, mice were fed sphingomyelin before and after tumor initiation. Both applications drastically reduced tumor formation, without a significant difference among the groups, indicating that sphingolipids are as effective in the chemoprevention of tumors as in early intervention. The normalization of cell proliferation and rate of apoptosis, but not the induction of differentiation, seem to be key players in the suppression of tumor formation by dietary sphingomyelin. This may have implications for the development of a cancer prevention or treatment strategy with sphingolipids as an alternative to conventional drugs. 相似文献
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Evasion of early cellular response mechanisms following low level radiation-induced DNA damage 总被引:9,自引:0,他引:9
Collis SJ Schwaninger JM Ntambi AJ Keller TW Nelson WG Dillehay LE Deweese TL 《The Journal of biological chemistry》2004,279(48):49624-49632
DNA damage that is not repaired with high fidelity can lead to chromosomal aberrations or mitotic cell death. To date, it is unclear what factors control the ultimate fate of a cell receiving low levels of DNA damage (i.e. survival at the risk of increased mutation or cell death). We investigated whether DNA damage could be introduced into human cells at a level and frequency that could evade detection by cellular sensors of DNA damage. To achieve this, we exposed cells to equivalent doses of ionizing radiation delivered at either a high dose rate (HDR) or a continuous low dose rate (LDR). We observed reduced activation of the DNA damage sensor ataxia-telangiectasia mutated (ATM) and its downstream target histone H2A variant (H2AX) following LDR compared with HDR exposures in both cancerous and normal human cells. This lack of DNA damage signaling was associated with increased amounts of cell killing following LDR exposures. Increased killing by LDR radiation has been previously termed the "inverse dose rate effect," an effect for which no clear molecular processes have been described. These LDR effects could be abrogated by the preactivation of ATM or simulated in HDR-treated cells by inhibiting ATM function. These data are the first to demonstrate that DNA damage introduced at a reduced rate does not activate the DNA damage sensor ATM and that failure to activate ATM-associated repair pathways contributes to the increased lethality of continuous LDR radiation exposures. This inactivation may reflect one strategy by which cells avoid accumulating mutations as a result of error-prone DNA repair and may have a broad range of implications for carcinogenesis and, potentially, the clinical treatment of solid tumors. 相似文献
8.
Dillehay BL Calvin DD Roth GW Hyde JA Kuldau GA Kratochvil RJ Russo JM Voight DG 《Journal of economic entomology》2005,98(1):103-112
Field studies in Pennsylvania and Maryland were conducted during 2000, 2001, and 2002 to test the applicability of published yield loss relationships developed in central Pennsylvania for European corn borer, Ostrinia nubilalis (Hübner), management in warmer, longer season corn, Zea mays L., grain production regions of the northeastern United States. Both isoline hybrids and non-Bt lead hybrids were compared against Bacillus thuringiensis (Bt) hybrids to measure effects of the pest on yield. The European corn borer economic analysis model was used to make site-specific predictions of loss per European corn borer larva for comparison with measured yield loss per larva. Although the model did not predict loss per larva at a field level, it did predict loss at a regional level. The model predicted an overall percentage of yield loss per larva of 2.69+/-0.12% over the region, which was similar to the measured yield loss per larva of 2.66+/-0.59% for isoline hybrids and 3.08+/-0.51% for lead hybrids. The model, on average, provided a good prediction of percentage of yield loss per larva within the climatic zones of 1100-1700 degree-days (DD) (base threshold 12.5 degrees C). Our results suggest that the yield loss relationship developed in Central Pennsylvania, when matched to the timing of third instar second generation European corn borer stalk tunneling is adequate for major corn grain production zones of the northeast United States. 相似文献
9.
High rate of DNA loss in the Drosophila melanogaster and Drosophila virilis species groups 总被引:6,自引:3,他引:3
We recently proposed that patterns of evolution of non-LTR
retrotransposable elements can be used to study patterns of spontaneous
mutation. Transposition of non-LTR retrotransposable elements commonly
results in creation of 5' truncated, "dead-on-arrival" copies. These
inactive copies are effectively pseudogenes and, according to the neutral
theory, their molecular evolution ought to reflect rates and patterns of
spontaneous mutation. Maximum parsimony can be used to separate the
evolution of active lineages of a non-LTR element from the fate of the
"dead-on-arrival" insertions and to directly assess the relative
frequencies of different types of spontaneous mutations. We applied this
approach using a non-LTR element, Helena, in the Drosophila virilis group
and have demonstrated a surprisingly high incidence of large deletions and
the virtual absence of insertions. Based on these results, we suggested
that Drosophila in general may exhibit a high rate of spontaneous large
deletions and have hypothesized that such a high rate of DNA loss may help
to explain the puzzling dearth of bona fide pseudogenes in Drosophila. We
also speculated that variation in the rate of spontaneous deletion may
contribute to the divergence of genome size in different taxa by affecting
the amount of superfluous "junk" DNA such as, for example, pseudogenes or
long introns. In this paper, we extend our analysis to the D. melanogaster
subgroup, which last shared a common ancestor with the D. virilis group
approximately 40 MYA. In a different region of the same transposable
element, Helena, we demonstrate that inactive copies accumulate deletions
in species of the D. melanogaster subgroup at a rate very similar to that
of the D. virilis group. These results strongly suggest that the high rate
of DNA loss is a general feature of Drosophila and not a peculiar property
of a particular stretch of DNA in a particular species group.
相似文献
10.
A model of cell killing by low-dose-rate radiation including repair of sublethal damage, G2 block, and cell division 总被引:2,自引:0,他引:2
L E Dillehay 《Radiation research》1990,124(2):201-207
A computer model that simulates the killing of exponentially growing cells by low-dose-rate radiation is described. The model incorporates cell killing by single-hit damage and double-hit (sublethal) damage, as well as repair of sublethal damage, delay of cell cycle progression, blockage and increased sensitivity of cells in the G2 phase of the cell cycle, and cell division. Seven cellular parameters determine the rate of cell killing. Initial estimates of most of these parameters can be made from independent experiments. Parameters were obtained that gave the best fit to the data for four cell lines, using constant or variable dose rates, and using as end points either the fraction of single cells forming colonies or the total number of clonogenic cells in a mass culture. Some of the parameters were determined to be insignificant or similar for the four cell lines. The main differences between the cell lines in patterns of cell killing over a range of dose rates appeared to be determined by differences in the values of four of the parameters. 相似文献