Methotrexate-induced morphological changes mimic those seen after heat shock

1989 ◽  
Vol 92 (1) ◽  
pp. 37-49
Author(s):  
D.A. Jackson ◽  
C.K. Pearson ◽  
D.C. Fraser ◽  
K.M. Prise ◽  
S.Y. Wong
Keyword(s):  
Heat Shock ◽  
Morphological Changes ◽  
Dna Strand Breaks ◽  
Chemotherapeutic Drug ◽  
General Stress Response ◽  
Strand Breaks ◽  
Nucleotide Pools ◽  
Concentration Changes ◽  
High Concentrations ◽  
Dna Strand

The survival of cells cultured in medium containing the chemotherapeutic drug methotrexate (MTX) is related directly to drug concentration. Changes in DNA resulting from a severe imbalance in the cells' nucleotide pools are thought to account for this cytotoxicity. We have attempted to clarify the gross biochemical changes that might lead to cell death. DNA strand breaks occur in cells treated with high concentrations of MTX but it is not clear that these are sufficient to account for cytotoxicity at lower doses. We observed dramatic changes in cytoskeletal morphology. Gross reorganization of the cytoskeleton is shown by immunolabelling but is high-lighted dramatically when cells are lysed to leave ‘nucleoids’. The nature of the changes seen in MTX-treated cells is characteristic of the cells’ general stress response, seen originally following heat shock. This study shows that other factors, such as changes in cytoskeletal function, must be considered together with any contribution from DNA damage, in order to account for the lethal effects of MTX.

scholarly journals Hyperthermia Activates a Subset of Ataxia-Telangiectasia Mutated Effectors Independent of DNA Strand Breaks and Heat Shock Protein 70 Status

2007 ◽  
Vol 67 (7) ◽  
pp. 3010-3017 ◽  
Author(s):  
Clayton R. Hunt ◽  
Raj K. Pandita ◽  
Andrei Laszlo ◽  
Ryuji Higashikubo ◽  
Manjula Agarwal ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Ataxia Telangiectasia ◽  
Heat Shock Protein 70 ◽  
Dna Strand Breaks ◽  
Ataxia Telangiectasia Mutated ◽  
Strand Breaks ◽  
Dna Strand

scholarly journals Toxicological Effects of Inorganic Nanoparticle Mixtures in Freshwater Mussels

Environments ◽  
2020 ◽  
Vol 7 (12) ◽  
pp. 109
Author(s):  
Joelle Auclair ◽  
Patrice Turcotte ◽  
Christian Gagnon ◽  
Caroline Peyrot ◽  
Kevin J. Wilkinson ◽  
...  
Keyword(s):  
Sublethal Effects ◽  
Morphological Changes ◽  
Freshwater Mussels ◽  
Aquatic Organisms ◽  
Exposure Period ◽  
Dna Strand Breaks ◽  
Dreissena Bugensis ◽  
Strand Breaks ◽  
Toxicological Effects ◽  
Dna Strand

The toxicological effects of nanoparticles mixtures in aquatic organisms are poorly understood. The purpose of this study was to examine the tissue metal loadings and sublethal effects of silver (nAg), cerium oxide (nCeO), copper oxide (nCuO) and zinc oxide (nZnO) nanoparticles individually at 50 µg/L and in two mixtures to freshwater mussels Dreissena bugensis. The mixtures consisted of 12.5 µg/L of each nanoparticle (Mix50) and 50 µg/L of each nanoparticles (Mix200). After a 96-h exposure period, mussels were analyzed for morphological changes, air time survival, bioaccumulation, inflammation (cyclooxygenase or COX activity), lipid peroxidation (LPO), DNA strand breaks, labile Zn, acetylcholinesterase (AChE) and protein–ubiquitin levels. The data revealed that mussels accumulated the nanoparticles with nCeO and nAg were the least and most bioavailable, respectively. Increased tissue metal loadings were observed for nCeO and nCuO in mixtures, while no mixture effects were observed for nAg and nZnO. The weight loss during air emersion was lower in mussels exposed to nCuO alone but not by the mixture. On the one hand, labile Zn levels was increased with nZnO but returned to control values with the Mix50 and Mix200, suggesting antagonism. On the other hand, DNA strand breaks were reduced for both mixtures compared to controls or to the nanoparticles individually, suggesting potentiation of effects. The same was found for protein–ubiquitin levels, which were decreased by nCeO and nCuO alone but not when in mixtures, which increased their levels. In conclusion, the data revealed that the behavior and effects of nanoparticles were influenced by other nanoparticles where antagonist and potentiation interactions were identified.

scholarly journals Long-term exposure to a 40-GHz electromagnetic field does not affect genotoxicity or heat shock protein expression in HCE-T or SRA01/04 cells

2019 ◽  
Vol 60 (4) ◽  
pp. 417-423 ◽  
Author(s):  
Shin Koyama ◽  
Eijiro Narita ◽  
Yukihisa Suzuki ◽  
Takeo Shiina ◽  
Masao Taki ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Protein Expression ◽  
Millimeter Waves ◽  
Dna Strand Breaks ◽  
Human Lens ◽  
Corneal Epithelial ◽  
Strand Breaks ◽  
Heat Shock Protein Expression ◽  
Dna Strand

AbstractMillimeter waves are used in various fields, and the risks of this wavelength range for human health must be carefully evaluated. In this study, we investigated the effects of millimeter waves on genotoxicity and heat shock protein expression in human corneal epithelial (HCE-T) and human lens epithelial (SRA01/04) cells. We exposed the cells to 40-GHz millimeter waves at 1 mW/cm2 for 24 h. We observed no statistically significant increase in the micronucleus (MN) frequency or the level of DNA strand breaks in cells exposed to 40-GHz millimeter waves relative to sham-exposed and incubator controls. Heat shock protein (Hsp) expression also exhibited no statistically significant response to the 40-GHz exposure. These results indicate that exposure to 40 GHz millimeter waves under these conditions has little or no effect on MN formation, DNA strand breaks, or Hsp expression in HCE-T or SRA01/04 cells.

scholarly journals Major DNA Fragmentation Is a Late Event in Apoptosis

1997 ◽  
Vol 45 (7) ◽  
pp. 923-934 ◽  
Author(s):  
Jae A. Collins ◽  
Cynthia A. Schandl ◽  
Kristy K. Young ◽  
Josef Vesely ◽  
Mark C. Willingham
Keyword(s):  
Dna Fragmentation ◽  
Morphological Changes ◽  
Cell Lysis ◽  
Dna Strand Breaks ◽  
Morphological Features ◽  
Nick Translation ◽  
Strand Breaks ◽  
In Situ Nick Translation ◽  
Dna Strand

Apoptosis, the terminal morphological and biochemical events of programmed cell death, is characterized by specific changes in cell surface and nuclear morphology. In addition, DNA fragmentation in an internucleosomal pattern is detectable in mass cultures of apoptotic cells. However, DNA fragmentation and nuclear morphological changes may not necessarily be associated events. In this study, we examined OVCAR-3 and KB human carcinoma cells using time-lapse video phase-contrast microscopy to characterize the surface and nuclear morphological features of apoptosis in response to treatment with either taxol or ricin. The surface morphological features of apoptosis were the same in both cell types and with both drugs. Using an in situ nick-translation histochemical assay, these single cells were also examined for DNA strand breaks during apoptosis. Surface morphological changes demonstrated discrete stages of cell rounding, surface blebbing, followed by cessation of movement and the extension of thin surface microspikes, followed much later by surface blistering and cell lysis. Nuclear features examined by DAPI cytochemistry demonstrated apoptotic nuclear condensation very early in this sequence, usually at the time of initial surface blebbing. The nick-translation assay, however, demonstrated DNA strand breaks at a much later time, only after the formation of separated apoptotic bodies or after final cell lysis. This study points out the differences between surface and nuclear morphological changes in apoptosis, and the large temporal separation between nuclear morphological changes and major DNA fragmentation detectable by this in situ technique. This result suggests caution in using in situ nick-translation as a direct correlate of internucleosomal DNA fragmentation in apoptosis.

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