Disruption of genomic integrity due to deficient DNA repair capacity and telomere shortening constitute hallmarks of malignant diseases. Incomplete or deficient repair of DNA double-strand breaks (DSB) is manifested by chromosomal aberrations and their frequency reflects inter-individual differences of response to exposure to mutagenic compounds. In this study, we investigated chromosomal integrity in peripheral blood lymphocytes (PBL) from newly diagnosed cancer patients, including 47 breast (BC) and 44 colorectal cancer (CRC) patients and 90 matched healthy controls. Mutagen sensitivity was evaluated by measuring chromatid breaks (CTAs) induced by bleomycin and supplemented by the chemiluminescent measurement of γ-H2AX phosphorylation in 19 cancer patients (11 BC, 8 CRC). Relative telomere length (RTL) was determined in 22 BC, 32 CRC, and 64 controls. We observed statistically significant increased level of CTAs (P = .03) and increased percentage of aberrant cells (ACs) with CTAs (P = .05) in CRC patients compared with controls after bleomycin treatment. No differences were observed between BC cases and corresponding controls. CRC and BC patients with shorter RTL (below median) exhibited significantly higher amount of ACs (P = .02), CTAs (P = .02), and cells with high frequency of CTAs (≥12 CTAs/PBL; P = .03) after bleomycin treatment. No such associations were observed in healthy controls. γ-H2AX phosphorylation after bleomycin treatment in PBL did not differ between CRC and BC patients. Our results suggest that altered DSB repair measured by sensitivity towards mutagen in PBL occurs particularly in CRC carcinogenesis. Irrespective of cancer type, telomere shortening may be associated with a decreased capacity to repair DSB.

• MeSH
• bleomycin škodlivé účinky   farmakologie   MeSH
• chromozomální aberace účinky léků   MeSH
• chromozomální poruchy patologie   MeSH
• chromozomy účinky léků   MeSH
• dospělí MeSH
• dvouřetězcové zlomy DNA účinky léků   MeSH
• kolorektální nádory genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfocyty MeSH
• nádory prsu genetika   metabolismus   MeSH
• oprava DNA účinky léků   MeSH
• pilotní projekty MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• telomery účinky léků   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• bleomycin MeSH

The moss Physcomitrella patens is unique for the high frequency of homologous recombination, haploid state, and filamentous growth during early stages of the vegetative growth, which makes it an excellent model plant to study DNA damage responses. We used single cell gel electrophoresis (comet) assay to determine kinetics of response to Bleomycin induced DNA oxidative damage and single and double strand breaks in wild type and mutant lig4 Physcomitrella lines. Moreover, APT gene when inactivated by induced mutations was used as selectable marker to ascertain mutational background at nucleotide level by sequencing of the APT locus. We show that extensive repair of DSBs occurs also in the absence of the functional LIG4, whereas repair of SSBs is seriously compromised. From analysis of induced mutations we conclude that their accumulation rather than remaining lesions in DNA and blocking progression through cell cycle is incompatible with normal plant growth and development and leads to sensitive phenotype.

• MeSH
• analýza jednotlivých buněk MeSH
• bleomycin farmakologie   MeSH
• buněčný cyklus genetika   MeSH
• haploidie * MeSH
• homologní rekombinace genetika   MeSH
• mechy genetika   růst a vývoj   MeSH
• mutace MeSH
• mutageneze genetika   MeSH
• mutageny farmakologie   MeSH
• oprava DNA genetika   MeSH
• oxidační stres účinky léků   MeSH
• poškození DNA účinky léků   MeSH
• regulace genové exprese u rostlin MeSH
• rostlinné proteiny biosyntéza   genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bleomycin MeSH
• mutageny MeSH
• rostlinné proteiny MeSH

In plants, different forms of programmed cell death (PCD) have been identified, but they only partially correspond to those described for animals, which is most probably due to structural differences between animal and plant cells. Here, the results show that in tobacco BY-2 cells, bleomycin (BLM), an inducer of double-strand breaks (DSBs), triggers a novel type of non-apoptotic PCD with paraptotic-like features. Analysis of numerous PCD markers revealed an extensive vacuolization, vacuolar rupture, and chromatin condensation, but no apoptotic DNA fragmentation, fragmentation of the nuclei, or sensitivity to caspase inhibitors. BLM-induced PCD was cell cycle regulated, occurring predominantly upon G(2)/M cell cycle checkpoint activation. In addition, this paraptotic-like PCD was at least partially inhibited by caffeine, a known inhibitor of DNA damage sensor kinases ATM and ATR. Interestingly, overexpression of one NtE2F transcriptional factor, whose homologues play a dual role in animal apoptosis and DNA repair, reduced PCD induction and modulated G(2)/M checkpoint activation in BY-2 cells. These observations provide a solid ground for further investigations into the paraptotic-like PCD in plants, which might represent an ancestral non-apoptotic form of PCD conserved among animals, protists, and plants.

• MeSH
• bleomycin farmakologie   MeSH
• buněčná smrt účinky léků   MeSH
• down regulace účinky léků   MeSH
• exprese genu účinky léků   MeSH
• fragmentace DNA účinky léků   MeSH
• kontrolní body buněčného cyklu účinky léků   MeSH
• protein-serin-threoninkinasy genetika   metabolismus   MeSH
• rostlinné proteiny genetika   metabolismus   MeSH
• tabák cytologie   účinky léků   genetika   metabolismus   MeSH
• transkripční faktory E2F genetika   metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bleomycin MeSH
• protein-serin-threoninkinasy MeSH
• rostlinné proteiny MeSH
• transkripční faktory E2F MeSH

DNA damage is a threat to genomic integrity in all living organisms. Plants and green algae are particularly susceptible to DNA damage especially that caused by UV light, due to their light dependency for photosynthesis. For survival of a plant, and other eukaryotic cells, it is essential for an organism to continuously check the integrity of its genetic material and, when damaged, to repair it immediately. Cells therefore utilize a DNA damage response pathway that is responsible for sensing, reacting to and repairing damaged DNA. We have studied the effect of 5-fluorodeoxyuridine, zeocin, caffeine and combinations of these on the cell cycle of the green alga Scenedesmus quadricauda. The cells delayed S phase and underwent a permanent G2 phase block if DNA metabolism was affected prior to S phase; the G2 phase block imposed by zeocin was partially abolished by caffeine. No cell cycle block was observed if the treatment with zeocin occurred in G2 phase and the cells divided normally. CDKA and CDKB kinases regulate mitosis in S. quadricauda; their kinase activities were inhibited by Wee1. CDKA, CDKB protein levels were stabilized in the presence of zeocin. In contrast, the protein level of Wee1 was unaffected by DNA perturbing treatments. Wee1 therefore does not appear to be involved in the DNA damage response in S. quadricauda. Our results imply a specific reaction to DNA damage in S. quadricauda, with no cell cycle arrest, after experiencing DNA damage during G2 phase.

• MeSH
• bleomycin farmakologie   MeSH
• buněčný cyklus účinky léků   genetika   MeSH
• Chlorophyta MeSH
• floxuridin farmakologie   MeSH
• G2 fáze genetika   MeSH
• kofein farmakologie   MeSH
• oprava DNA účinky léků   MeSH
• poškození DNA fyziologie   MeSH
• proteiny buněčného cyklu MeSH
• Scenedesmus cytologie   genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bleomycin MeSH
• floxuridin MeSH
• kofein MeSH
• proteiny buněčného cyklu MeSH
• Zeocin MeSH Prohlížeč

DNA double strand breaks (DSBs) are one of the most cytotoxic forms of DNA damage and must be repaired by recombination, predominantly via non-homologous joining of DNA ends (NHEJ) in higher eukaryotes. However, analysis of DSB repair kinetics of plant NHEJ mutants atlig4-4 and atku80 with the neutral comet assay shows that alternative DSB repair pathways are active. Surprisingly, these kinetic measurements show that DSB repair was faster in the NHEJ mutant lines than in wild-type Arabidopsis. Here we provide the first characterization of this KU-independent, rapid DSB repair pathway operating in Arabidopsis. The alternate pathway that rapidly removes the majority of DSBs present in nuclear DNA depends upon structural maintenance of chromosomes (SMC) complex proteins, namely MIM/AtRAD18 and AtRAD21.1. An absolute requirement for SMC proteins and kleisin for rapid repair of DSBs in Arabidopsis opens new insight into the mechanism of DSB removal in plants.

• MeSH
• antibiotika antitumorózní farmakologie   MeSH
• Arabidopsis účinky léků   genetika   metabolismus   MeSH
• bleomycin farmakologie   MeSH
• časové faktory MeSH
• chromozomální proteiny, nehistonové fyziologie   MeSH
• chromozomy rostlin chemie   metabolismus   MeSH
• DNA rostlinná účinky léků   metabolismus   MeSH
• dvouřetězcové zlomy DNA účinky léků   MeSH
• fragmentace DNA účinky léků   MeSH
• kometový test MeSH
• oprava DNA fyziologie   MeSH
• proteiny huseníčku fyziologie   MeSH
• rekombinace genetická fyziologie   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibiotika antitumorózní MeSH
• bleomycin MeSH
• chromozomální proteiny, nehistonové MeSH
• DNA rostlinná MeSH
• MIM protein, Arabidopsis MeSH Prohlížeč
• proteiny huseníčku MeSH
• RAD21.1 protein, Arabidopsis MeSH Prohlížeč

Yeast cell viability was evaluated microscopically following exposure to heat shock for 30 min at 53 degrees C. The cells were previously grown in the presence of potential stressors (anticancer drugs; e.g., 5-fluorouracil, methotrexate, cisplatin, bleomycin, mitomycin-C and camptothecin-11). The induction of thermotolerance was documented by significantly increased viability after heat shock. This effect, which was reversed by cycloheximide, was comparable to that observed following exposure to a mild heat stress. These data demonstrate that pretreatment with sub-toxic concentrations of some of the clinically used antineoplastic agents conferres thermotolerance to yeast, possibly through the synthesis of protein components.

• MeSH
• antitumorózní látky farmakologie   MeSH
• bleomycin farmakologie   MeSH
• cisplatina farmakologie   MeSH
• fluorouracil farmakologie   MeSH
• irinotekan MeSH
• kamptothecin analogy a deriváty   farmakologie   MeSH
• methotrexát farmakologie   MeSH
• mitomycin farmakologie   MeSH
• Saccharomyces účinky léků   fyziologie   MeSH
• vysoká teplota * MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antitumorózní látky MeSH
• bleomycin MeSH
• cisplatina MeSH
• fluorouracil MeSH
• irinotekan MeSH
• kamptothecin MeSH
• methotrexát MeSH
• mitomycin MeSH

The adaptive response and reciprocal adaptive response induced in vitro by exposure to low doses of gamma rays (0.05 Gy) or bleomycin (0.05 microg/ml) in human peripheral blood lymphocytes were assessed by the frequency of chromosome aberrations. Gamma rays (1.5 Gy) or bleomycin (1.5 microg/ml) were used as the challenge doses. In the experiments, blood samples from 5 healthy donors were investigated. It has been found that low doses of bleomycin and gamma rays induced a reciprocal adaptive response to high doses of gamma rays or bleomycin. Moreover, the results confirmed that the adaptive response did not correlate with the radiosensitivity of the peripheral blood lymphocytes.

• MeSH
• antibakteriální látky farmakologie   MeSH
• biologická adaptace * MeSH
• bleomycin farmakologie   MeSH
• lidé MeSH
• lymfocyty účinky léků   fyziologie   účinky záření   MeSH
• záření gama MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• antibakteriální látky MeSH
• bleomycin MeSH

G2 chromosomal sensitivity to bleomycin (30 micrograms/ml) was tested in PHA-stimulated lymphocytes of healthy subjects and in patients with familial and sporadic tumors. These were multiple endocrine neoplasias (MEN) types 1, 2A and 2B, familial medullar thyroid cancer, Recklinghausen neurofibromatosis type I, sporadic and hereditary malignant tumors, and a preleukemic disorder, the myelodysplastic syndrome. Control subjects were either young (15-20), middle-aged (28-49) or old (70-83 years). Cells from old healthy subjects and from subjects with MEN 1 showed increased sensitivity to clastogenic effects of bleomycin. All the remaining investigated groups were insignificantly different from controls. Our data suggest that in contrast with recessively inherited syndromes with chromosome instability the mutagen hypersensitivity, as evaluated by the extent of chromosomal damage, is not a feature of most dominantly inherited tumor syndromes.

• MeSH
• bleomycin farmakologie   MeSH
• chromatidy účinky léků   MeSH
• chromozomální aberace * MeSH
• dědičné nádorové syndromy genetika   MeSH
• dítě MeSH
• dominantní geny * MeSH
• dospělí MeSH
• G2 fáze MeSH
• kultivované buňky MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mnohočetné endokrinní neoplazie genetika   MeSH
• myelodysplastické syndromy genetika   MeSH
• nádory štítné žlázy genetika   MeSH
• neurofibromatóza 1 genetika   MeSH
• poškození DNA MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bleomycin MeSH

The reduction of vanadate (+5V) to vanadyl (+4V) was demonstrated by ESR spectra in the presence of methylene-blue, chlorpromazine, imipramine and dosulepin, but not in the presence of benzodiazepines and Li+. Bleomycine forms an (inactive) complex with +4V which may explain the disinhibition of the brain microsomal Na+-K+ ATPase in the presence of vanadyl. The reduction of +5V to +4V by antidepressants would diminish the binding of +5V to the ATPase and could account for some of the therapeutic action of the drugs in manic-depressive illness.

• MeSH
• bleomycin farmakologie   MeSH
• chlorpromazin farmakologie   MeSH
• dothiepin farmakologie   MeSH
• imipramin farmakologie   MeSH
• mozek enzymologie   MeSH
• myši MeSH
• oxidace-redukce MeSH
• psychotropní léky farmakologie   MeSH
• sodíko-draslíková ATPasa metabolismus   MeSH
• techniky in vitro MeSH
• vanad metabolismus   MeSH
• vanadáty MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bleomycin MeSH
• chlorpromazin MeSH
• dothiepin MeSH
• imipramin MeSH
• psychotropní léky MeSH
• sodíko-draslíková ATPasa MeSH
• vanad MeSH
• vanadáty MeSH

• MeSH
• adeninnukleotidy metabolismus   MeSH
• adenosindifosfát farmakologie   MeSH
• adhezivita trombocytů účinky léků   MeSH
• amidiny farmakologie   MeSH
• antitumorózní látky farmakologie   terapeutické užití   MeSH
• Aspirin farmakologie   terapeutické užití   MeSH
• bleomycin farmakologie   MeSH
• buněčná membrána účinky léků   MeSH
• cyklofosfamid farmakologie   MeSH
• fluorouracil farmakologie   MeSH
• glyoxal farmakologie   MeSH
• hydrazony farmakologie   MeSH
• kombinovaná farmakoterapie MeSH
• lidé MeSH
• methotrexát farmakologie   MeSH
• nádory krev   farmakoterapie   MeSH
• triazichon MeSH
• trombocyty účinky léků   metabolismus   MeSH
• vinca alkaloidy farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adeninnukleotidy MeSH
• adenosindifosfát MeSH
• amidiny MeSH
• antitumorózní látky MeSH
• Aspirin MeSH
• bleomycin MeSH
• cyklofosfamid MeSH
• fluorouracil MeSH
• glyoxal MeSH
• hydrazony MeSH
• methotrexát MeSH
• triazichon MeSH
• vinca alkaloidy MeSH