Metabolism of arsenic in Drosophila melanogaster and the genotoxicity of dimethylarsinic acid in the Drosophila wing spot test.
Inorganic arsenic is nongenotoxic in the Drosophila melanogaster wing somatic mutation and recombination test (SMART). Recent evidence in mammalian systems indicates that methylated metabolites of arsenic are more genotoxic than inorganic arsenic. Thus, we hypothesized that inorganic arsenic is nongenotoxic in Drosophila because they are unable to biotransform arsenic to methylated forms. In the present study, we fed trivalent and pentavalent inorganic arsenic to Drosophila larvae and adults and measured the production of methylated derivatives. No biomethylated arsenic species were found in the organisms or in the growth medium, which suggests that Drosophila are unable to biomethylate inorganic arsenic. Exposure of Drosophila to the methylated arsenic derivative dimethylarsinic acid (DMA(V)) resulted in incorporation of this organoarsenic compound without demethylation. In addition, we used the SMART wing spot assay, which measures loss of heterozygosity (LOH) resulting from gene mutation, chromosomal rearrangement, chromosome breakage, and chromosome loss, to evaluate the genotoxicity of DMA. DMA by itself induced significant increases in the frequency of total spots, small spots, and large single spots. These results are consistent with the important role of arsenic biomethylation as a determinant of the genotoxicity of arsenic compounds. The absence of biomethylation in Drosophila could explain the lack of genotoxicity for inorganic arsenic and the genotoxicity of methylated arsenic species in the SMART wing spot assay.
Rizki
Mostapha
M
Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, Spain.
Kossatz
Elk
E
Velázquez
Antonia
A
Creus
Amadeu
A
Farina
Massimo
M
Fortaner
Salvador
S
Sabbioni
Enrico
E
Marcos
Ricardo
R
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D020261:Arsenic Poisoning; D001152:Arsenicals; D002101:Cacodylic Acid / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004330:Drosophila; D004331:Drosophila melanogaster / Q000187:drug effects*; D005260:Female; D017344:Genes, Insect; D019656:Loss of Heterozygosity; D008297:Male; D008745:Methylation; D009152:Mutagenicity Tests; D009153:Mutagens; D013997:Time Factors; D014921:Wings, Animal / Q000187:drug effects*
D001152:Arsenicals; D009153:Mutagens; D002101:Cacodylic Acid; D001151:Arsenic