zinostatin and Bloom-Syndrome

Chromosome aberrations and sister-chromatid exchanges (SCEs) were examined in 4 ataxia telangiectasia (AT)-derived B-lymphoblastoid cell lines (B-LCLs) (AT-S, AT-SHI, AT-SHI B13A and AsHa) following treatments with neocarzinostatin (NCS) and bleomycin. All of these cell lines exhibited extremely high frequencies of chromosome aberrations with the NCS and bleomycin treatments. Among them, AsHa, a mutant B-LCL originating from an AT patient, showed high frequencies of SCEs under high bromodeoxyuridine (BrdU) concentrations retaining hypersensitivity to NCS and bleomycin with regard to chromosome aberrations. A clear BrdU dose-dependent increase in SCEs (9.85 SCEs/cell at 40 micrograms/ml, 36.65 SCEs/cell at 100 micrograms/ml on average) in this mutant was observed. When AsHa mutant cells were treated with NCS (0.02 microgram/ml) and/or bleomycin (5.0 micrograms/ml) under 40 micrograms/ml BrdU (minimum BrdU concentration for sister-chromatid differential staining), SCE levels increased from 9.85 (baseline level) to 21.1 with NCS and 20.5 with bleomycin, in a dose-dependent manner. These observations indicate that AsHa is a unique AT-derived mutant cell clone with a high SCE character retaining the original hypersensitivity to bleomycin and NCS.

Topics: Antibiotics, Antineoplastic; Ataxia Telangiectasia; B-Lymphocytes; Bleomycin; Bloom Syndrome; Bromodeoxyuridine; Cell Division; Cell Line; Chromosome Aberrations; Dose-Response Relationship, Drug; Humans; Mutation; Sister Chromatid Exchange; Zinostatin