title: Arsenic trioxide mutational spectrum analysis in the mouse lymphoma assay.
abstract: 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 4h with 10microM 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.
authors.affiliation: Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Edifici Cn, Universitat Autònoma de Barcelona, 08193 Bellaterra, Cerdanyola del Vallès, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Soriano
authors.forename: Amadeu
authors.initials: A
authors.lastname: Creus
authors.forename: Ricard
authors.initials: R
authors.lastname: Marcos
mesh_terms: D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals; D001681:Biological Assay; D045744:Cell Line, Tumor; D007940:Leukemia L5178 / Q000235:genetics; D015473:Leukemia, Promyelocytic, Acute / Q000235:genetics; D051379:Mice; D009152:Mutagenicity Tests; D010087:Oxides / Q000633:toxicity*; D013057:Spectrum Analysis; D013937:Thymidine Kinase / Q000235:genetics
chemical_list: D001152:Arsenicals; D010087:Oxides; D013937:Thymidine Kinase; D000077237:Arsenic Trioxide