169 research outputs found
Analysis of chromosome positions in the interphase nucleus of Chinese hamster cells by laser-UV-microirradiation experiments
Unsynchronized cells of an essentially diploid strain of female Chinese hamster cells derived from lung tissue (CHL) were laser-UV-microirradiated (=257 nm) in the nucleus either at its central part or at its periphery. After 7–9 h postincubation with 0.5 mM caffeine, chromosome preparations were made in situ. Twenty-one and 29 metaphase spreads, respectively, with partial chromosome shattering (PCS) obtained after micro-irradiation at these two nuclear sites, were Q-banded and analyzed in detail. A positive correlation was observed between the frequency of damage of chromosomes and both their DNA content and length at metaphase. No significant difference was observed between the frequencies of damage obtained for individual chromosomes at either site of microirradiation. The frequency of joint damage of homologous chromosomes was low as compared to nonhomologous ones. Considerable variation was noted in different cells in the combinations of jointly shattered chromosomes. Evidence which justifies an interpretation of these data in terms of an interphase arrangement of chromosome territories is discussed. Our data strongly argue against somatic pairing as a regular event, and suggest a considerable variability of chromosome positions in different nuclei. However, present data do not exclude the possibility of certain non-random chromosomal arrangements in CHL-nuclei. The interphase chromosome distribution revealed by these experiments is compared with centromere-centromere, centromere-center and angle analyses of metaphase spreads and the relationship between interphase and metaphase arrangements of chromosomes is discussed
Decreased transcription-coupled nucleotide excision repair capacity is associated with increased p53- and MLH1-independent apoptosis in response to cisplatin
Abstract
Background
One of the most commonly used classes of anti-cancer drugs presently in clinical practice is the platinum-based drugs, including cisplatin. The efficacy of cisplatin therapy is often limited by the emergence of resistant tumours following treatment. Cisplatin resistance is multi-factorial but can be associated with increased DNA repair capacity, mutations in p53 or loss of DNA mismatch repair capacity.
Methods
RNA interference (RNAi) was used to reduce the transcription-coupled nucleotide excision repair (TC-NER) capacity of several prostate and colorectal carcinoma cell lines with specific defects in p53 and/or DNA mismatch repair. The effect of small inhibitory RNAs designed to target the CSB (Cockayne syndrome group B) transcript on TC-NER and the sensitivity of cells to cisplatin-induced apoptosis was determined.
Results
These prostate and colon cancer cell lines were initially TC-NER proficient and RNAi against CSB significantly reduced their DNA repair capacity. Decreased TC-NER capacity was associated with an increase in the sensitivity of tumour cells to cisplatin-induced apoptosis, even in p53 null and DNA mismatch repair-deficient cell lines.
Conclusion
The present work indicates that CSB and TC-NER play a prominent role in determining the sensitivity of tumour cells to cisplatin even in the absence of p53 and DNA mismatch repair. These results further suggest that CSB represents a potential target for cancer therapy that may be important to overcome resistance to cisplatin in the clinic
Classification of advanced stages of Parkinson’s disease: translation into stratified treatments
Untersuchungen über die Einwirkung von Röntgenstrahlen auf Erythrozyten und ihre Bedeutung für die Ausbildung einer Anämie nach Ganzkörperbestrahlung / Studies of the effect of x-rays on erythrocytes and its significance in the development of anemia after total body irradiation
Über die Ausbildung einer Anämie nach einmaliger kurzzeitiger Ganzkörperbestrahlung mit Röntgenstrahlen beim Kaninchen / Development of anemia after single short-term total body irradiation with x-ray in rabbits
Die normale Lebenszeit und die Kinetik des Auf- und Abbaus der Erythrozyten beim Kaninchen / The normal life span and kinetics of the structure and degeneration of erythrocytes in the rabbit
Untersuchungen über die Einwirkung von Röntgenstrahlen auf Erythrozyten und ihre Bedeutung für die Ausbildung einer Anämie nach Ganzkörperbestrahlung
Units of transcription for cytoplasmic RNA in mouse myeloma cells.
The size of transcription units for several of the abundant cytoplasmic mRNA species in mouse myeloma cells has been analyzed by the ultraviolet light mapping technique. Inactivation kinetics and target size analyses for production of the predominant RNA species indicate that the mRNAs originate in precursor molecules that are 2--14 times larger than the mature mRNA. This estimate of the size of the transcription unit may be a minimum one since it would not take into account promoter-distal sequences if these were not necessary for processing of the mRNA precursor
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