TY - JOUR
T1 - Arsenic trioxide mutational spectrum analysis in the mouse lymphoma assay
AU - Soriano, Carolina
AU - Creus, Amadeu
AU - Marcos, Ricard
N1 - Funding Information:
Carolina Soriano is supported by a postgraduate fellowship from the Generalitat de Catalunya. This investigation has been supported in part by the Spanish Ministry of Education and Science (CAICYT, SAF2008-02933) and by the Generalitat de Catalunya (CIRIT, 2005SGR-00136).
PY - 2008/11/10
Y1 - 2008/11/10
N2 - It has been well documented that long-term exposure to inorganic arsenic induces cancers and vascular diseases in a dose-response relationship. Nevertheless, arsenic has also demonstrated to have anticancer activity; thus, arsenic trioxide (ATO, As2O3) is an inorganic trivalent arsenic form, currently used in the treatment against acute promyelocytic leukaemia (APL). The open discussion about how arsenic compounds induce genotoxic damage has moved us to evaluate the mutational spectrum induced by ATO in mouse lymphoma cells. Thus, 49 Tk-/- mutant colonies obtained in the mouse lymphoma assay (MLA), after treatments lasting for 4 h with 10 μM ATO, and 49 spontaneous mutant colonies from independent untreated cultures, were used to analyse and to characterise the mutational spectrum induced by this arsenic compound, to understand its mechanism of action. RT-PCR analysis of Tk cDNA and PCR amplifications of eight selected microsatellite sequences, located on chromosome 11, were used to carry out this screening. Our results show that, in mouse lymphoma cells, ATO is a strong clastogenic compound inducing large deletions, at chromosomal level, covering the Tk gene, as well as other regions of chromosome 11.
AB - It has been well documented that long-term exposure to inorganic arsenic induces cancers and vascular diseases in a dose-response relationship. Nevertheless, arsenic has also demonstrated to have anticancer activity; thus, arsenic trioxide (ATO, As2O3) is an inorganic trivalent arsenic form, currently used in the treatment against acute promyelocytic leukaemia (APL). The open discussion about how arsenic compounds induce genotoxic damage has moved us to evaluate the mutational spectrum induced by ATO in mouse lymphoma cells. Thus, 49 Tk-/- mutant colonies obtained in the mouse lymphoma assay (MLA), after treatments lasting for 4 h with 10 μM ATO, and 49 spontaneous mutant colonies from independent untreated cultures, were used to analyse and to characterise the mutational spectrum induced by this arsenic compound, to understand its mechanism of action. RT-PCR analysis of Tk cDNA and PCR amplifications of eight selected microsatellite sequences, located on chromosome 11, were used to carry out this screening. Our results show that, in mouse lymphoma cells, ATO is a strong clastogenic compound inducing large deletions, at chromosomal level, covering the Tk gene, as well as other regions of chromosome 11.
KW - Arsenic trioxide (ATO, AsO)
KW - Mouse lymphoma assay
KW - Mutational spectrum
KW - Tk locus
UR - http://www.scopus.com/inward/record.url?scp=54149117788&partnerID=8YFLogxK
U2 - 10.1016/j.mrfmmm.2008.08.014
DO - 10.1016/j.mrfmmm.2008.08.014
M3 - Article
C2 - 18822301
AN - SCOPUS:54149117788
SN - 0027-5107
VL - 646
SP - 1
EP - 7
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -