Endogenous annexin A1 counter-regulates bleomycin-induced lung fibrosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Bleomycin sensitivity in patients with familial and sporadic polyposis: a pilot study

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of turmeric and its active principle, curcumin, on bleomycin-induced chromosome aberrations in Chinese hamster ovary cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Differential susceptibility to chromatid breaks induced by bleomycin in sub-fertile and fertile bovines

The rate of chromatid breaks was studied in cows with a history of sub-fertility by means of a test based on measurement of the average of breaks induced in lymphocytes of peripheral blood cultures. Fourteen female specimens were divided into two groups: fertile and sub-fertile. Peripheral blood lymphocytes were cultured and prepared for cytogenetic analysis. Two types of culture were established for each animal to evaluate the response of peripheral blood lymphocyte cultures to the genotoxic effects of bleomycin. The first culture did not receive bleomycin treatment (spontaneous chromosome aberrations). Our results showed that median breaks per cell (b/c) (+/-semirange) for spontaneous culture of the fertile and sub-fertile animals and bleomycin sensitivity assay for fertile and sub-fertile animals were 0.00 +/- 0.06, 0.02 +/- 0.03, 0.08 +/- 0.05 and 0.22 +/- 0.09, respectively. There was no significant difference (P > 0.05) in the chromosomal breakage in lymphocytes not exposed to bleomycin; however, in comparing the number of chromatid breaks per cell in cultures treated with bleomycin, the sub-fertile group showed a significantly higher (P < 0.05) level than the fertile group. These findings have implications both for identifying cattle with less than optimum fertility as well as for providing potential avenues to study the origins of sub-fertility. (C) 2004 Elsevier B.V. All rights reserved.

Genetic susceptibility to bleomycin: A twin study

The frequency of chromatid breaks was analysed in peripheral lymphocytes obtained from sixteen healthy monozygotic (MZ) and sixteen healthy dizygotic (DZ) pairs of twins. In addition, increases in the frequency of chromatid breaks, following in vitro treatment of whole blood with 0.03 unit/ml bleomycin (BLM), were analysed in the same twins. There was a highly significant intrapair difference in the variance of the frequency of chromatid breaks among MZ and DZ twins, before and after BLM treatment. The coefficient of heritability was 85,5% and it was concluded that genetic factors contributed significantly to the individual variation observed in BLM induced chromatid break rates.

Chromosome sensitivity to bleomycin in G2 lymphocytes from Down syndrome patients

Several studies have demonstrated that lymphocytes from patients with Down syndrome (DS) exhibit an increased frequency of chromosome aberrations when they are exposed to ionizing radiation or to chemicals at the G0 or G1 phases of the cell cycle, but not at G2 when compared to normal subjects. To determine the susceptibility of DS lymphocytes at G2 phase, bleomycin, a radiomimetic agent, was used to induce DNA breaks in blood cultures from 24 Down syndrome patients. All the patients with DS showed free trisomy 21 (47,XX + 21 or 47,XY + 21). Individuals that showed an average number of chromatid breaks per cell higher than 0.8 were considered sensitive to the drug. No control child showed susceptibility to bleomycin, and among the 24 patients with DS, only one was sensitive to the drug. No significant difference was observed between the two groups, regarding chromatid break frequencies in treated G2 lymphocytes. The distribution of bleomycin-induced breaks in each group of chromosomes was similar for DS and controls. No significant difference was found in the response to bleomycin between male and female subjects. Probably, the main factor involved in chromosome sensitivity of lymphocytes from patients with DS is the phase of the cell cycle in which the cell is treated.

Evaluation of the antigenotoxicity of polysaccharides and beta-glucans from Agaricus blazei, a model study with the single cell gel electrophoresis/Hep G2 assay

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

AVALIACAO DO EFEITO DO VENENO DE APIS MELLIFERA EM CULTURAS DE E. COLI, S. TYPHIMURIUM E Y. ENTEROCOLITICA TRATADAS COM BLEOMICINA

Apis mellifera bee venom (Africanized honey bee) was tested for the ability to protect against the lethal effect of bleomycin, an antibiotic and antineoplastic agent. Since the radioprotective effect of the venom has been observed on the other biological systems, in the present study the venom was applied to cultures of enterobacteria treated with bleomycin, a radiomimetic agent. The venom did not act as a protective agent against bleomycin in E. coli, S. typhimurium or Y. enterocolitica.

Liposomal daunorubicin and dexamethasone as a treatment for multiple myeloma - The DD protocol

Context and Objective: Lipasomial daunorubicin has been used to treat hematological malignancies, including multiple myelomo (MM). The goal was to evaluate efficacy, side-effects and toxicity of liposomal daunorubicin and dexamethasone (DD Protocol). Design and Setting: Prospective study of Sírio-Libonês, São Camilo, Brasil and Alemão Oswaldo Cruz hospitals. Methods: Twenty consecutive patients with active MM received four cycles of liposomal daunorubicin intravenously for two hours (25-30 mg/m 2/day) on three consecutive days per month, with oral dexamethasone, (10 mg every six hours) on four consecutive days three times a month. Results: The male/female ratio was 1:1 and median age 60. Nine patients were stage IIA, ten IIIA and one IIIB. The median from diagnosis to starting DD was 13 months. All patients received four cycles, except one. Fifteen had already received chemotherapy before DD. Responses of > 50% reduction in serum monoclonal paraprotein were observed in six patients after first cycle (30%), six after second (30%) and four after third (20%), while four (20%) did not obtain this. Initially, 17 patients (85%) had anemia: 12 (70%) achieved correction. Progressive disease was observed in three patients (15%), while one had minimal response, four (20%) partial and 12 (60%) complete. Hemotologlical toxicity was acceptable: three patients (15%) had neutrophils < 1,000/mm 3; none had thrombocyfopenia. Gastrointestinal toxicity was mild: nausea (10%), anorexio (15%) and no vomiting. Conclusions: This treatment has mild toxicity and good response rate. It may therefore be feasible before autologous bone marraw transplantation.

Contribuição da terapia celular com células tronco em fibrose em ratos

Pós-graduação em Pesquisa e Desenvolvimento (Biotecnologia Médica) - FMB

Remodelamento parenquimatoso pulmonar em dois modelos experimentais de fibrose

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Association among XRCC1, XRCC3, and BLHX gene polymorphisms and chromosome instability in lymphocytes from patients with endometriosis and ovarian cancer

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The Th17 pathway in the peripheral lung microenvironment interacts with expression of collagen V in the late state of experimental pulmonary fibrosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Relationship between head and neck cancer therapy and some genetic endpoints

Head and neck cancer (HNC) is the sixth most common human malignancy worldwide. The main forms of treatment for HNC are surgery, radiotherapy (RT) and chemotherapy (CT). However, the choice of therapy depends on the tumor staging and approaches, which are aimed at organ preservation. Because of systemic RT and CT genotoxicity, one of the important side effects is a secondary cancer that can result from the activity of radiation and antineoplastic drugs on healthy cells. Ionizing radiation can affect the DNA, causing single and double-strand breaks, DNA-protein crosslinks and oxidative damage. The severity of radiotoxicity can be directly associated with the radiation dosimetry and the dose-volume differences. Regarding CT, cisplatin is still the standard protocol for the treatment of squamous cell carcinoma, the most common cancer located in the oral cavity. However, simultaneous treatment with cisplatin, bleomycin and 5-fluorouracil or treatment with paclitaxel and cisplatin are also used. These drugs can interact with the DNA, causing DNA crosslinks, double and single-strand breaks and changes in gene expression. Currently, the late effects of therapy have become a recurring problem, mainly due to the increased survival of HNC patients. Herein, we present an update of the systemic activity of RT and CT for HNC, with a focus on their toxicogenetic and toxicogenomic effects.