The 1:1 Cu(II) complexes of bleomycin (BLM) A2, BLM B2, epi-BLM B2, iso-BLM B2, depyruvamide-BLM A2, deglyco-BLM B2 and the structurally related peptides (P-5m, P-3A and P-3) have been comprehensively investigated by ESR and electrochemical methods. ESR spectra for Cu(II) complexes of BLM A2, epi-BLM B2, depyruvamide-BLM A2 and P-3 revealed the axially symmetric g-anisotropies. In contrast, ESR...

A sensitive new method to assay bleomycin (BLM) metabolism was developed using an ion-paired, reverse-phase high-pressure liquid chromatography technique in conjunction with fluorescence detection that allowed levels of BLM less than 20 ng/ml to be detected. The metabolism of bleomycin B2 in homogenates from benign and malignant human tumors was studied, and all 14 tumors were capable of metabo...

Bleomycin (BLM) as an anti-cancer agent causes tissue toxicities through DNA damaging and cell deaths. The aim of this study was to investigate the effects of thymol against genotoxicity and anti-proliferation induced by BLM in normal human lymphocytes and ovarian cancer cells. Peripheral blood samples were collected from human volunteers and were incubated with thymol at different concentratio...

Metabolic inactivation of bleomycin (BLM) by cysteine proteinase-like enzymes is thought to be a major mechanism of BLM tumor resistance. We now report that the human colon carcinoma COLO-205 is highly resistant to BLM and that E-64, a cysteine proteinase inhibitor, sensitizes COLO-205 to BLM. Treatment of COLO-205-bearing nude mice with either E-64 (40 mg/kg) or BLM (10 mg/kg) alone did not in...

Introduction: Due to interesting therapeutic properties of 46Sc and antineoblastic antibiotic, bleomycin (BLM), 46Sc-bleomycin (46Sc-BLM) was developed as a possible therapeutic compound. Methods: In this work, Sc-46 chloride was obtained by thermal neutron flux (4 × 1013 n.cm-2.s-1) of natural metallic scandium sample followed ...

A Bloom's deficient mouse model (Blm(m3/m3)) has been shown to induce colorectal tumorigenesis when crossed with Apc+/Min mice. Here, we investigated whether the Blm(m3/m3) genotype could induce tumorigenesis in extracolonic tissues in tuberous sclerosis 1-deficient (Tsc1+/-) mice that are predisposed to renal cystadenomas and carcinomas. Genotyping of offspring from Tsc1+/- Blm+/m3 intercrosse...

BLM helicase, the protein mutated in Bloom syndrome, is involved in signal transduction cascades after DNA damage. BLM is phosphorylated on multiple residues by different kinases either after stress induction or during mitosis. Here, we have provided evidence that both Chk1 and Chk2 phosphorylated the NH(2)-terminal 660 amino acids of BLM. An internal region within the DExH motif of BLM negativ...

Three bleomycin (BLM)-resistant sublines were isolated from a human head and neck squamous cell carcinoma cell line (A-253); these sublines (C-10, D-10, and G-11) were 4-, 9-, and 21-fold resistant to BLM A2, respectively. These sublines were selectively resistant to other members of the BLM class, namely BLM B2, peplomycin, talisomycin S10b, and bleomycinic acid; none of the sublines displayed...

Bloom syndrome helicase (BLM) has key roles in homologous recombination repair, telomere maintenance, and DNA replication. Germ-line mutations in the BLM gene causes Bloom syndrome, a rare disorder characterized by premature aging and predisposition to multiple cancers, including breast cancer. The clinicopathologic significance of BLM in sporadic breast cancers is unknown. We investigated BLM ...