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PubMed1980

Therapy of solid Walker carcinosarcoma 256 with bleomycin after synchronization with hydroxyurea.

Rats with the solid Walker carcinosarcoma 256 were synchronized with hydroxyurea (6 x 50 mg/kg or 1 x 300 mg/kg body weight) and treated with bleomycin (32 mg/kg body weight) at different time points thereafter. Bleomycin clearly affects Walker carcinosarcoma cells at the G1/S boundary or in S-phase. The improvement in the results of bleomycin therapy after pretreatment with hydroxyurea can mainly be accounted for by the synchronization of the tumour cells.

Animals↗
PubMed1983

An experimental study of enhanced cell killing by hyperthermia and bleomycin.

In vitro cell killing effects from heating and/or bleomycin have been investigated using the KK-47 cell line derived from a human bladder carcinoma and the colony-forming assay system. Percent survivals of the asynchronous cells heated to 40 degrees, 41 degrees, 42 degrees and 43 degrees C for 30 min were 96.6%, 93.3%, 91.4% and 71.2%, respectively, and those at 43 degrees C for 2h were 80.6%, 75.5%, 46.0% and 1.4%, respectively. The survival percentages of the cells treated with bleomycin at the concentrations of 1, 3, 6 and 10 micrograms per ml at 37 degrees C for 30 min were 66.0%, 40.4%, 21.9% and 11.9%, respectively. When hyperthermia at 43 degrees C was combined with bleomycin, a greatly enhanced cell killing effect was obtained by preheating and simultaneous heating as compared with the effect of post-heating.

Bleomycin↗
PubMed1995

Induced mutagenesis by bleomycin in the purple sulfur bacterium Thiocapsa roseopersicina.

Cell death and mutagenesis in bleomycin-treated cells of Thiocapsa roseopersicina (a purple sulfur bacterium) was studied by cultivation in a semisolid medium (agar-shake technique). This technique has also proven useful in assessing the frequency of antibiotic mutations by detecting and counting individual colonies of Thiocapsa roseopersicina. The frequencies of spontaneous mutants resistant to ampicillin, rifampicin, cloramphenicol, tetracycline, kanamycin, streptomycin, and neomycin were also studied: they ranged between 2 x 10(-9) and 9 x 10(-8). Bleomycin (4 micrograms/ml) sharply increased the frequency of ampicillin-resistant mutants, from 10(-8) (spontaneous) to 4 x 10(-4) (induced), in 17 h. An inducible, error-prone mechanism of DNA synthesis seems to be responsible for this enhancement of the mutagenic effect. this is the first report on the sensitivity to several antibiotics, and capacity of lethality and mutagenesis by bleomycin has been studied in a purple sulfur bacterium.

Ampicillin Resistance↗
PubMed1976

Effect of bleomycin on the fine structure of mouse fibroblasts.

Asynchronously dividing mouse fibroblasts (L-cells) treated with the antitumour antibiotic Bleomycin show various rather specific morphological alterations. Many of the cells exposed to bleomycin assume a more or less epitheloid cell shape and are larger than untreated cells; in addition to an increase in nuclear size these cells often contain multiple nuclei. In most of the cells nuclei show an almost complete loss of peripheral condensed chromatin. The nucleolar hypertrophy initially observed is followed by a shrinkage and segregation of the nucleolar components. The cytoplasmic alterations include dilatation of the cisternae of the rough endoplasmic reticulum as well as an increase of free, non membrane attached ribosomes, often arranged in spiral- and rosette-shaped polysomes; they are not specific for bleomycin.

Animals↗
PubMed1989

Effect of N-acetylcysteine on the antiproliferative action of X-rays or bleomycin in cultured human lung tumor cells.

N-Acetylcysteine is currently being considered as a possible selective protector against pulmonary toxicity resulting from X-rays or chemotherapeutic treatment, but its clinical application awaits evidence that it does not interfere with the efficient killing of tumor cells. The capacity of N-acetylcysteine to protect against the antitumor activity of X-rays and of bleomycin was evaluated in a clonogenic cell-survival assay using SW-1573 human squamous lung carcinoma cells as a tumor model. Using the highest non-toxic dose of N-acetylcysteine (incubation for 2 days in the continuous presence of 10 mM) no effect on clonogenic cell killing by X-rays or bleomycin treatment could be detected, even though a twofold enhancement of endogenous glutathione was effectuated. Our data thus indicate that clinically relevant concentrations of N-acetylcysteine are incapable of protecting tumor cells against clonogenic killing by X-rays and by bleomycin.

Acetylcysteine↗
PubMed1976

[Formation of giant cells in oral squamous cell carcinoma during bleomycin treatment: enzymehistochemical, electronmicroscopic and ultrahistochemical investigations (author's transl)].

During treatment of keratinizing squamous cell carcinomas with bleomycin tumor cells are devitalized by keratinization, while simple necrosis plays a minor role. Connected with this process is a marked resorptive granulomatous inflammation with numerous macrophages which is followed by a fibrous organization. In the border region of the keratinized tumor areas many multinucleated giant cells appear. The nature of these giant cells was the subject of controversy. Enzyme histochemical, electronmicroscopic, and ultrahistochemical investigations in three cases of advanced squamous cell carcinoma of the oral cavity prove that the giant cells which are formed during bleomycin treatment are not multinucleated tumor cells, but multinucleated macrophages. The enzymatic pattern is similar to macrophages with a high content of acid phosphatase and aminopeptidase. The ultrastructure of the giant cells is characterized by lysosomes with acid phosphatase activity, pinocytotic vesicles, and cytoplasmic projections on the cell surface with signs of macroendocytosis. The tumor cells show an epithelial differentiation with desmosomes, tonofibrils, and keratohyaline granula. The giant cells are formed by fusion of mononucleated (monocytogenic) macrophages. The fusions seem to be related to the functional status of the cells. It is possible, that the macrophages and the giant cells have an additional immunologic function. This is suggested by the frequent association of giant cells with lymphocytes. The importance of these facts for the evaluation of the action of bleomycin and the consequences for its therapeutic use are discussed. A combination with methods causing a dedifferentiation of the tumor or suppression of the immunologic defense seems to be problematic.

Acid Phosphatase↗
PubMed1987

Heat shock phenomena in Aspergillus nidulans. II. Combined effect of heat and bleomycin to heat shock protein synthesis, survival rate and induction of mutations.

The combined action of hyperthermia and Bleomycin on Aspergillus nidulans was studied at three different levels: mycelial protein synthesis, spore viability and induction of mutations. It was found that Bleomycin treatment of preincubated mycelia during the heat shock enhances the incorporation of 35S-methionine into heat shock bands. Furthermore, simultaneous treatment with hyperthermia (43 degrees C) and Bleomycin results in greater cytotoxic activity in spores and in a higher induction rate of point mutations.

Aspergillus nidulans↗
PubMed1988

Intranuclear differences in the response of Purkinje cell DNA of the rat cerebellum to bleomycin. A microphotometric and autoradiographic study.

A single dose of the DNA-binding cytostatic agent bleomycin (100 micrograms/g body weight, subcutaneously) was given to 10-day-old rats to study unscheduled repair DNA synthesis in nucleolar and in bulk nuclear chromatin of postmitotic Purkinje neurons. The Feulgen reaction and Hoechst 33342 staining were used for quantitative evaluation of nuclear DNA content and chromatin structure. The repair synthesis of DNA was detected by 3H-thymidine autoradiography. The data showed a lesser staining of Purkinje as well as granule cell DNA by Hoechst 33342 in bleomycin-treated animals than in controls, but there was no difference in staining with the Feulgen reaction. The mechanisms of DNA staining by both cytochemical methods suggest that bleomycin reacted preferentially with AT-rich and single stranded DNA in cerebellar cells in vivo. Weak 3H-thymidine labelling was found in Purkinje cells of both control and treated rats, but in the latter group the labelling was more pronounced near or over the nucleolus. The enhanced unscheduled DNA synthesis in the nucleolar region of Purkinje cells of treated animals may be due to greater damage of DNA in this region or may indicate a greater ability of the nucleolar chromatin to repair its DNA.

Animals↗
PubMed1979

Chemical and biological properties of bleomycin labelled with 57Co.

The chemical composition of bleomycin labelled with 57Co and its distribution and kinetics in the organs of tumour bearing rats were studied. For separating bleomycin, the chromatography on a CM-Sephadex C-25 column with a gradient of ammonium formate was found to be most suitable. It is also possible to use paper chromatography in 10% NH4Cl and thin layer chromatography in 10% ammonium acetate with methyl alcohol 1:1. The fractions obtained by the chromatographic separation were identified as A2, B2 and A1. Labelling with 57Co given rise to a more complicated mixture of labelled compounds, all of them differing chromatographically from the original non-labelled components. Using carrier-free 57Co two main radioactive compounds are formed apparently corresponding to the fractions A2 and B2 containing one atom of Co per molecule. The amount of another two labelled components grows progressively with increasing amount of carrier CoCl2. Since their chromatographic properties are even more different from those of the original compounds, it was concluded that they probably contain two atoms of Co in their molecules. During distribution studies, rapid excretion of labelled bleomycin into the urine and stool was observed. Increased activities were retained in the liver, kidney, intestine and tumour.

Animals↗
PubMed1991

Multivesicular liposomes containing bleomycin for subcutaneous administration.

Optimal cancer treatment with cell-cycle-specific agents requires maintenance of a cytotoxic drug level for a prolonged period. We explored the use of multivesicular liposomes as a slow-release depot of bleomycin for systemic administration via the s.c. route. The average volume-adjusted liposome size was 19.1 microns, the half-life of leakage in human plasma was 32.1 h, and the half-life of s.c. liposomal bleomycin was 31.8 h. When tested against the s.c. B-16 melanoma model in BDF1 mice, the therapeutic index of single-dose bleomycin given s.c. was significantly improved when the drug was encapsulated in multivesicular liposomes. The efficacy was improved as assessed by both inhibition of tumor growth and increased life span, and the toxicity appeared to be decreased.

Animals↗
PubMed1992

Gene expression in ataxia telangiectasia cells as perturbed by bleomycin treatment.

The autosomal recessive genetic disorder ataxia telangiectasia (AT) has been characterized in the RNA transcripts of cultured cells. Molecular species of poly (A)+ RNA that are present in AT fibroblasts (ATFs) at levels different from those in normal human fibroblasts (NHFs) were cloned in the form of cDNAs. Treatment with bleomycin, which transiently inhibits DNA synthesis in NHFs but not in ATFs, differentiated ATFs and NHFs in the above cloning. Two cDNA clones with an identical DNA sequence were isolated, the corresponding RNA transcript of which was induced approximately twofold after bleomycin treatment in NHFs, but not in ATFs. The DNA sequence of these two cDNA clones, except for its polyadenylation part, was identical to the heavy-strand replication origin sequence of human mitochondrial DNA. The results indicate the possibility that the induction of this RNA transcript is involved in bleomycin-induced inhibition of DNA synthesis in normal human cells, while it is defective in AT cells. In addition, the previous observation that much fibronectin is produced in AT cells was confirmed in this study in terms of RNA transcription.

Ataxia Telangiectasia↗
PubMed1990

Bleomycin-induced chromosomal damage in tuberous sclerosis.

To investigate the possible involvement of mutagen-induced chromosomal instability in tuberous sclerosis the blood lymphocytes obtained from eleven patients with this disease and eleven healthy controls of comparable age and sex were exposed to bleomycin in vitro during the late S and G2 phases of the cell cycle. Neither the spontaneous aberration yields nor the bleomycin-induced chromosomal sensitivity differed between the two groups. The chromosomal distribution of 578 and 478 induced breaks in patients and controls, respectively, was similar. Thus, bleomycin-induced G2 chromosomal hypersensitivity in lymphocytes of patients with tuberous sclerosis is not an intrinsic feature of this hereditary disease.

Adolescent↗
PubMed1990

Cytogenetic characterization of 20 lymphoblastoid lines derived from human individuals differing in bleomycin sensitivity.

Forty lymphoblastoid (lymphoid) lines were established from 42 volunteer blood donors, including healthy individuals and patients with head and neck carcinomas. Each peripheral blood sample was split into two portions, one for the establishment of a lymphoid line and the other for short-term culture, which was used to estimate bleomycin sensitivity by cytogenetic procedures. Twenty lymphoid lines were selected at random to compare bleomycin sensitivity with data obtained from short-term lymphocyte cultures. In each set, bleomycin sensitivity of lymphoid cells was similar to that of the lymphocytes. The lymphoid lines, which can be propagated for an unlimited supply of relatively homogeneous cellular material, will be useful for a variety of future investigations.

Bleomycin↗
PubMed1980

Bleomycin and subsequent anaesthesia: a retrospective study at Vancouver General Hospital.

A retrospective review was made of 20 surgical procedures in 14 patients with testicular carcinoma, previously treated with bleomycin chemotherapy, to evaluate the incidence of postoperative pulmonary complications. Other studies have suggested an increased rate of pulmonary complications, including fatal respiratory failure, when inspired oxygen fraction (FIO2) exceeds 0.3 during or after operation. There is a suggestion that bleomycin may sensitize the lungs to the effect of oxygen, leading to oxygen toxicity. This study involved patients whose inspired oxygen fraction ranged from 0.3 to 1.0 and only one non-fatal pulmonary complication occurred. The risks of anaesthesia following bleomycin are discussed with particular reference to possible enhanced oxygen toxicity.

Anesthesia↗
PubMed2001

[Bleomycin prick in therapy-resistant verruca vulgaris].

Common warts can be highly resistant to conventional treatments such as cryotherapy, laser surgery, salicylic acid and mechanical removal. Intralesional bleomycin has been described as an effective treatment for common warts since 1970. We treated a 27-year-old woman with Sharp's syndrome who was on immunosuppressive drugs and had suffered for nine years from therapy-resistant warts on palms and soles. A bleomycin-prick technique using a bifurcated needle to introduce bleomycin sulfate (1 mg/ml sterile saline solution) into the warts resulted in almost complete remission after 16 treatment sessions.

Adult↗
PubMed1996

IS431mec-mediated integration of a bleomycin-resistance gene into the chromosome of a methicillin-resistant Staphylococcus aureus strain isolated in Japan.

A methicillin-resistant Staphylococcus aureus (MRSA) strain B-26, isolated clinically in Hiroshima University Hospital, is resistant to bleomycin together with kanamycin. In the present study, we analysed the nucleotide sequence of the 5.1-kb HindIII fragment containing the bleomycin- and kanamycin-resistance genes, which were previously cloned [Bhuiyan et al. (1995) Appl Microbiol Biotechnol 43: 65-69] from the chromosomal DNA of MRSA B-26. The present study found that the DNA sequence contains the duplicated target sequence (GATTAGAT) consisting of 8 bp for transposase and the entire nucleotide sequence of the plasmid pUB110, together with the sequence of inverted repeats (16 bp), designated IR-r and IR-1 in IS431 mec. The 8-bp duplication sequence, produced by the transposable element, was first found by us. We proposed that bleomycin resistance in MRSA B-26 is attributed to the IS431 mec-mediated integration of pUB110 into the chromosome.

Bacterial Proteins↗
PubMed2006

Multicenter phase II study of the CyclOBEAP (CHOP-like + etoposide and bleomycin) regimen for patients with poor-prognosis aggressive lymphoma.

Our aim was to study the efficacy of the addition of etoposide and bleomycin to a [cyclophosphamide (CPA), doxorubicin (DXR), vincristine (VCR), and prednisone (PDN)] CHOP-like regimen for the treatment of aggressive lymphoma. The CyclOBEAP regimen was administered over a total period of 12 weeks. Doxorubicin, 50 mg/m(2), was given every 2 weeks in combination with either cyclophosphamide, 1,000 mg/m(2), (weeks 1, 5, 9) or etoposide, 70 mg/m(2) qd x4 (weeks 3, 7, 11). During the alternate weeks, non-myelosuppressive vincristine, 1.4 mg/m(2) (maximum, 2.0 mg/body), was given either with bleomycin, 10 mg/m(2) (weeks 2, 6, 10), or alone (weeks 4,8,12). Prednisolone, 40 mg/m(2), was administered daily for 14 days during weeks 1-2, 5-6, and 9-10. There were 121 eligible patients and median age of 51 years. A complete response was achieved in 106 patients (88%) and a partial response in 11 patients. The 5-year overall survival (OS) rate was 72% and progression-free survival (PFS) rate was 62%. When the patients were divided according to the International Prognostic Index (IPI), the 5-year OS and PFS rates did not significantly differ among risk groups. When the patients with DLBCL were divided according to the IPI, the 5-year OS and PFS rates also did not significantly differ. World Health Organization (WHO) grade 4 neutropenia was observed in 91 patients and thrombocytopenia in 13 patients. No treatment-related deaths were observed. The addition of etoposide and bleomycin to CHOP therapy may enhance the effect of CHOP therapy for aggressive lymphoma. We will perform a prospective study of CyclOBEAP regimen combined with rituximab and test its safety and efficacy.

Adolescent↗
PubMed2005

In situ assessment of oxidant and nitrogenic stress in bleomycin pulmonary fibrosis.

Reactive oxygen species (ROS) and nitric oxide (NO) have a role in the development of pulmonary fibrosis after bleomycin administration. The ROS production induces an antioxidant response, involving superoxide dismutases (SODs), catalase, and glutathione peroxidases. We compared in situ oxidative burden and antioxidant enzyme activity in bleomycin-injured rat lungs and normal controls. ROS expression and catalase, glucose-6-phosphate-dehydrogenase (G6PHD), and NOS/NADPH-diaphorase activity were investigated by using histochemical reactions. Nitric oxide synthase (e-NOS and i-NOS) and SOD (MnSOD, Cu/ZnSOD, ECSOD) expression was investigated immunohistochemically. After treatment ROS production was enhanced in both phagocytes and in type II alveolar epithelial cells. Mn, Cu/Zn, and ECSOD were overexpressed in parenchymal cells, whereas interstitium expressed ECSOD. Catalase and G6PHD activity was moderately increased in parenchymal and inflammatory cells. NOS/NADPH-d activity and i-NOS expression increased in alveolar and bronchiolar epithelia and in inflammatory cells. It can be suggested that the concomitant activation of antioxidant enzymes is not adequate to scavenge the oxidant burden induced by bleomycin lung damage. Inflammatory cells and also epithelial cells are responsible of ROS and NO production. This oxidative and nitrosative stress may be a substantial trigger in TGF-beta1 overexpression by activated type II pneumocytes, leading to fibrotic lesions.

Animals↗