Assessment of the genotoxicity of atenolol in human peripheral blood lymphocytes: correlation between chromosomal fragility and content of micronuclei.
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.
Télez
Mercedes
M
Dpto. Genética, Antropología Física y Fisiología Animal, Facultad de Ciencia y Tecnología, Universidad del País Vasco, Bilbao, Spain.
Ortiz-Lastra
Eduardo
E
Gonzalez
Adolfo J
AJ
Flores
Piedad
P
Huerta
Iratxe
I
Ramírez
Juan M
JM
Barasoain
Maitane
M
Criado
Begoña
B
Arrieta
Isabel
I
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000633:toxicity*; D001262:Atenolol / Q000633:toxicity*; D016022:Case-Control Studies; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility / Q000187:drug effects*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008214:Lymphocytes / Q000187:drug effects*; D008297:Male; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects*; D015162:Micronucleus Tests; D008875:Middle Aged
D000959:Antihypertensive Agents; D001262:Atenolol