Evaluation of the cytogenetic damage induced by the antihypertensive drug nimodipine in human lymphocytes.
The aim of this work was a study of the genotoxic potential of chronic long-term therapy with the antihypertensive drug nimodipine by measures of sister chromatid exchanges (SCE) and micronuclei (MN) in peripheral human lymphocytes of patients with long-term exposure to this drug. Peripheral human lymphocytes of control individuals exposed in vitro to nimodipine were also studied to assess the effect of the drug itself. Fluorescence in situ hybridization (FISH) with a centromeric probe was performed to determine the origin of the induced MN. The in vivo study was carried out on five patients under antihypertensive treatment with nimodipine. The in vitro study was performed on five control individuals by adding the drug to the culture medium at a final concentration similar to the levels found in plasma (controls/medium). The in vivo study showed no genotoxic effects of long-term therapy with nimodipine because the frequencies of SCE and MN in exposed patients did not show significant differences as compared with control individuals. A statistically significant increase in the frequency of MN was detected in controls/medium as compared with control individuals without the drug. FISH analysis revealed statistically significant differences with respect to the frequency of centromeric signals in nimodipine-induced MN in vitro. With regard to the in vivo results, chronic long-term therapy with nimodipine is not associated with increased genotoxicity. The differing results in vivo and in vitro could be due to extensive metabolism of nimodipine, indicating that the cytogenetic effect observed was due to the drug itself rather than its metabolites or to an adaptive response to nimodipine in vivo.
Télez
M
M
Departamento Biología Animal y Genética, Facultad de Ciencias, Universidad del País Vasco, Apartado 644, 48080 Bilbao, Spain. ggbtesem@lg.ehu.es
Martínez
B
B
Criado
B
B
Ortega
B
B
Peñagarikano
O
O
Flores
P
P
Ortiz-Lastra
E
E
Arrieta
I
I
D000368:Aged; D000369:Aged, 80 and over; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D002503:Centromere / Q000187:drug effects / Q000235:genetics; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects*; D008297:Male; D015162:Micronucleus Tests; D009153:Mutagens; D009553:Nimodipine / Q000494:pharmacology* / Q000627:therapeutic use; D012016:Reference Values; D012854:Sister Chromatid Exchange / Q000187:drug effects*
D000959:Antihypertensive Agents; D009153:Mutagens; D009553:Nimodipine