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Assessment of the genotoxicity of atenolol in human peripheral blood lymphocytes: Correlation between chromosomal fragility and content of micronuclei
Authors:Mercedes Télez  Eduardo Ortiz-Lastra  Adolfo J Gonzalez  Piedad Flores  Iratxe Huerta  Juan M Ramírez  Maitane Barasoain  Begoña Criado  Isabel Arrieta
Institution:1. Dpto. Genética, Antropología Física y Fisiología Animal, Facultad de Ciencia y Tecnología, Universidad del País Vasco, Bilbao, Spain;2. Dpto. Especialidades Médico-quirúrgicas, Facultad de Medicina y Odontología, Universidad del País Vasco, Bilbao, Spain;3. Dpto. de Medicina Interna, Facultad de Medicina y Odontología, Universidad del País Vasco, Bilbao, Spain;4. Dpto. de Farmacología Clínica y Dietética, Escuela de Enfermería, Universidad del País Vasco, Bilbao, Spain;5. Cooperativa de Ensino Superior Politecnico e Universitario, Porto, Portugal
Abstract:The antihypertensive drug atenolol was found to induce chromosome loss, detected as micronuclei in the peripheral lymphocytes of treated patients. The fundamental question which chromosomes the micronuclei were derived from remains to be answered. Analysis of structural chromosomal aberrations (CAs) and expression of fragile sites (FS) were pursued in this study. They revealed a significantly higher incidence of chromosomal aberrations (chromatid and chromosome breaks) in patients compared with controls, where 10 FS emerged as specific. Also, the band 17q12–21, where known fragile sites have not been reported, was only expressed in atenolol-treated patients. Fluorescence in situ hybridization using chromosome-specific probes revealed the preferential involvement of chromosomes 7, 11, 17 and X in the micronuclei (MN) of patients. The results also suggest a correlation between chromosomal fragility and content of MN, and support the findings for a linkage between hypertension and a locus on chromosome 17.
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