PMID- 10792010
OWN - NLM
STAT- MEDLINE
DCOM- 20000721
LR  - 20190513
IS  - 0267-8357 (Print)
IS  - 0267-8357 (Linking)
VI  - 15
IP  - 3
DP  - 2000 May
TI  - In vitro and in vivo evaluation of the antihypertensive drug atenolol in cultured 
      human lymphocytes: effects of long-term therapy.
PG  - 195-202
AB  - The genotoxicity of atenolol, a beta-blocker antihypertensive drug, both in vitro 
      and in vivo, was cytogenetically tested for its ability to induce sister 
      chromatid exchange (SCE) and micronuclei (MN) in cultured peripheral lymphocytes. 
      Also, 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 the one hand, on four patients under antihypertensive treatment 
      with atenolol and, on the other hand, on four matched control individuals taking 
      an oral dose of atenolol. The in vitro study was performed on the control 
      individuals by adding the drug to the culture medium at a final concentration 
      similar to the levels found in plasma. When a comparison was made, the frequency 
      of SCE did not show significant differences in any case. A statistically 
      significant increase in the frequency of MN was detected in patients but not in 
      control individuals either in vitro or in vivo. FISH analysis revealed 
      statistically significant differences between patients and control individuals 
      without the drug with respect to the frequency of centromeric signals in MN. 
      Taking all these observations together, our data suggest that chronic exposure to 
      atenolol resulted mainly in the induction of chromosome loss, so an aneugenic 
      activity could be predicted. Different sensitivity to the compound was observed 
      among control individuals. Nevertheless, all of them responded to the presence of 
      atenolol in the same way in both assays. Interindividual variability was also 
      reported. The intervariability seen in patients suggested an adaptive response to 
      the chemical after long-term therapy.
FAU - Telez, M
AU  - Telez M
AD  - Departamento Biologia Animal y Genetica, Facultad de Ciencias, Universidad del 
      Pais Vasco, Bilbao, Spain. ggbtesem@lg.ehu.es
FAU - Martinez, B
AU  - Martinez B
FAU - Criado, B
AU  - Criado B
FAU - Lostao, C M
AU  - Lostao CM
FAU - Penagarikano, O
AU  - Penagarikano O
FAU - Ortega, B
AU  - Ortega B
FAU - Flores, P
AU  - Flores P
FAU - Ortiz-Lastra, E
AU  - Ortiz-Lastra E
FAU - Alonso, R M
AU  - Alonso RM
FAU - Jimenez, R M
AU  - Jimenez RM
FAU - Arrieta, I
AU  - Arrieta I
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Mutagenesis
JT  - Mutagenesis
JID - 8707812
RN  - 0 (Antihypertensive Agents)
RN  - 0 (Mutagens)
RN  - 50VV3VW0TI (Atenolol)
SB  - IM
MH  - Antihypertensive Agents/*pharmacology/therapeutic use
MH  - Atenolol/*pharmacology/therapeutic use
MH  - Cells, Cultured
MH  - Centromere/drug effects/genetics
MH  - Humans
MH  - Hypertension/blood/*drug therapy/genetics
MH  - In Situ Hybridization, Fluorescence
MH  - Lymphocytes/cytology/*drug effects
MH  - *Micronucleus Tests
MH  - *Mutagens
MH  - Reference Values
MH  - Sister Chromatid Exchange/*drug effects
EDAT- 2000/05/03 09:00
MHDA- 2000/08/01 11:00
CRDT- 2000/05/03 09:00
PHST- 2000/05/03 09:00 [pubmed]
PHST- 2000/08/01 11:00 [medline]
PHST- 2000/05/03 09:00 [entrez]
AID - 10.1093/mutage/15.3.195 [doi]
PST - ppublish
SO  - Mutagenesis. 2000 May;15(3):195-202. doi: 10.1093/mutage/15.3.195.