A subline of B16 melanoma cells which is 10-fold resistant to bleomycin (BLM) was developed by exposure of the parental cell line to sequential increases in BLM concentration. This resistance to BLM is stable for over 30 passages in drug-free medium. Neither double minute chromosomes nor homogeneously staining regions were evident in karyotypes of the resistant cells. The subline, B16/BLM-R1, w...

The bleomycins (BLMs) are a family of natural glycopeptides used clinically as antitumor agents. In the presence of required cofactors (Fe(2+) and O(2)), BLM causes both single-stranded (ss) and double-stranded (ds) DNA damage with the latter thought to be the major source of cytotoxicity. Previous biochemical and structural studies have demonstrated that BLM can mediate ss cleavage through mul...

The spectrum of tumors that arise owing to the overexpression of c-Myc and loss of BLM is very similar. Hence, it was hypothesized that the presence of BLM negatively regulates c-Myc functions. By using multiple isogenic cell lines, we observed that the decrease of endogenous c-Myc levels that occurs in the presence of BLM is reversed when the cells are treated with proteasome inhibitors, indic...

Characteristics of the reaction of bleomycin-A2 (BLM) and several of its metal complexes with Ehrlich cells in culture are described. Short incubation of BLM and Fe(III)-, Cu-, Zn-, and CdBLM with Ehrlich cells effectively inhibits cell proliferation. There is a sharp break at 30 min in the dependence of cytotoxicity upon time of exposure of cells to these forms of the drug. Qualitatively, the ...

Bleomycin (BLM) induces lung inflammation and subsequent fibrosis in humans and animal models. We hypothesized that monocytes-macrophages represent target cells for BLM toxicity and participate in the initial stages of pulmonary inflammation. We developed an animal model of early lung lesions using systemic administration of BLM (2 U.100 g-1 body weight over 5 days) (BLM-rats). We observed a si...

Chain breakage in DMA induced by bleomycin A (BLM) was enhanced more than 150-fold by the reduced nicotinamide adenine dinucleotide phosphate-dependent elec tron transport system of rat liver microsomes. However, the enhancement effect on DMA was partially reduced by the preincubation of BLM with the microsomal systems. BLM-Cu2' was found to stimulate considerably micro somal reduced nicotinami...

Mutation of the Bloom's syndrome (BS) gene, BLM, results in genomic instability. As the first step toward positional cloning of the gene, tight linkage of BLM and FES at 15q26.1 was detected by genotyping affected in families in which the parents are cousins, so-called homozygosity mapping. Linkage disequilibrium between BLM and FES was detected in Ashkenazi Jews with BS, confirming the linkage...

Bleomycin (BLM) is a useful anticancer agent sometimes associated with a diffuse pulmonary inflammation and fibrosis. Using an intratracheal model of BLM-induced pulmonary damage, we have further inves tigated alveolar macrophage (AM) activation following intratracheal BLM. From rats that had been treated with either a single, fibrogenic, intratracheal dose of BLM (BLM-AM) or a comparable volum...

Bleomycin (BLM) is a useful anticancer agent sometimes associated with a diffuse pulmonary inflammation and fibrosis. Using an intratracheal model of BLM-induced pulmonary damage, we have further investigated alveolar macrophage (AM) activation following intratracheal BLM. From rats that had been treated with either a single, fibrogenic, intratracheal dose of BLM (BLM-AM) or a comparable volume...

backgrounds: bleomycin (blm) has been labeled with radioisotopes and widely used in therapy and diagnosis. in this study blm was labeled with [62zn] zinc chloride for oncologic pet studies. materials and methods: the complex was obtained at the ph=2 in normal saline at 90 ° c in 60 min. radio-tlc showed an overall radiochemical yield of 95-97% (radiochemical purity > 97%). stability of complex ...