PMID- 24755253
OWN - NLM
STAT- MEDLINE
DCOM- 20141209
LR  - 20141013
IS  - 1879-3592 (Electronic)
IS  - 1383-5718 (Linking)
VI  - 767
DP  - 2014 Jun
TI  - Genotoxic evaluation of five Angiotesin II receptor blockers: in vivo and in 
      vitro micronucleus assay.
PG  - 1-7
LID - S1383-5718(14)00099-0 [pii]
LID - 10.1016/j.mrgentox.2014.04.005 [doi]
AB  - Angiotensin II receptor blockers (ARBs) are a new class of drugs for the 
      treatment of hypertension. In this study, we studied the potential genotoxic 
      effects of five ARBs in vivo and in vitro in human peripheral blood lymphocytes 
      (PBLs) by means of the cytokinesis-block micronucleous (CBMN) assay in 
      combination with fluorescence in situ hybridization (FISH) with a centromeric 
      probe. The nuclear division index (NDI) was used as a measure of cytotoxicity. We 
      also analyzed the association between sex, age, duration of treatment and MN 
      formation. The in vivo study was carried out in 55 hypertensive patients. The in 
      vitro study was performed in 10 control individuals by adding the drugs to the 
      culture medium at a final concentration similar to the levels found in plasma in 
      patients. Our results showed a significant increase in the frequencies of MN and 
      binucleated cells with MN (BNMN) in vivo and especially in vitro. We observed 
      variability in the mean frequency of MN and BNMN among the five drugs analyzed. 
      In vivo, patients treated with Candesartan, Telmisartan and Valsartan showed a 
      statistical significant increase in these parameters, while Olmesartan showed the 
      highest effect in vitro. We also found that the drugs inhibit the NDI in vitro 
      and that Eprosartan, Olmesartan and Telmisartan are the ARBs studied with the 
      highest effect in decreasing the proliferation of the cells. FISH analysis 
      revealed no significant difference between patients and controls in the frequency 
      of centromeric signals. A slight variability, without statistical significance, 
      in the frequency of micronuclei with a centromere signal (CN(+)MN) was found 
      among the different ARBs analyzed, ruling out an aneugenic potential. When 
      accounting for risk factors, we found that in patients there is a positive 
      correlation between MN, BNMN and sex and a negative correlation with duration of 
      treatment.
CI  - Copyright (c) 2014 Elsevier B.V. All rights reserved.
FAU - Huerta, Iratxe
AU  - Huerta I
AD  - Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of 
      Science and Technology, University of the Basque Country, Bilbao, Spain; Genetic 
      Laboratory, Bilbao, Spain.
FAU - Barasoain, Maitane
AU  - Barasoain M
AD  - Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of 
      Science and Technology, University of the Basque Country, Bilbao, Spain.
FAU - Telez, Mercedes
AU  - Telez M
AD  - Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of 
      Science and Technology, University of the Basque Country, Bilbao, Spain; Genetic 
      Laboratory, Bilbao, Spain.
FAU - Longa, Mikel
AU  - Longa M
AD  - Virgen de Begona Laboratories (Medikosta), Erandio, Bizkaia, Spain.
FAU - Muga, Javier
AU  - Muga J
AD  - Virgen de Begona Laboratories (Medikosta), Erandio, Bizkaia, Spain.
FAU - Barrenetxea, Gorka
AU  - Barrenetxea G
AD  - Department of Medical-Surgical Specialties, Faculty of Medicine, University of 
      the Basque Country, Bilbao, Spain.
FAU - Ortiz-Lastra, Eduardo
AU  - Ortiz-Lastra E
AD  - Department of Medical-Surgical Specialties, Faculty of Medicine, University of 
      the Basque Country, Bilbao, Spain.
FAU - Gonzalez, Javier
AU  - Gonzalez J
AD  - Department of Medical-Surgical Specialties, Faculty of Medicine, University of 
      the Basque Country, Bilbao, Spain.
FAU - Criado, Begona
AU  - Criado B
AD  - Cooperativa de Ensino Superior Politecnico e Universitario (CESPU), Porto, 
      Portugal.
FAU - Arrieta, Isabel
AU  - Arrieta I
AD  - Department of Genetics, Physical Anthropology and Animal Physiology, Faculty of 
      Science and Technology, University of the Basque Country, Bilbao, Spain. 
      Electronic address: mariaisabel.arrieta@ehu.es.
LA  - eng
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140419
PL  - Netherlands
TA  - Mutat Res Genet Toxicol Environ Mutagen
JT  - Mutation research. Genetic toxicology and environmental mutagenesis
JID - 101632149
RN  - 0 (Angiotensin Receptor Antagonists)
SB  - IM
MH  - Aged
MH  - Angiotensin Receptor Antagonists/*adverse effects/pharmacology
MH  - Cell Proliferation/*drug effects
MH  - Cells, Cultured
MH  - Centromere/metabolism/pathology
MH  - *DNA Damage
MH  - Female
MH  - Humans
MH  - Hypertension/drug therapy/metabolism
MH  - In Situ Hybridization, Fluorescence
MH  - Leukocytes, Mononuclear/*metabolism/pathology
MH  - Male
MH  - Micronuclei, Chromosome-Defective/*chemically induced
MH  - Middle Aged
OTO - NOTNLM
OT  - Angiotensin II receptor blockers
OT  - FISH
OT  - Genotoxicity
OT  - Micronuclei
EDAT- 2014/04/24 06:00
MHDA- 2014/12/15 06:00
CRDT- 2014/04/24 06:00
PHST- 2014/01/15 00:00 [received]
PHST- 2014/04/03 00:00 [revised]
PHST- 2014/04/10 00:00 [accepted]
PHST- 2014/04/24 06:00 [entrez]
PHST- 2014/04/24 06:00 [pubmed]
PHST- 2014/12/15 06:00 [medline]
AID - S1383-5718(14)00099-0 [pii]
AID - 10.1016/j.mrgentox.2014.04.005 [doi]
PST - ppublish
SO  - Mutat Res Genet Toxicol Environ Mutagen. 2014 Jun;767:1-7. doi: 
      10.1016/j.mrgentox.2014.04.005. Epub 2014 Apr 19.