Influence of mus201 and mus308 mutations of Drosophila melanogaster on the genotoxicity of model chemicals in somatic cells in vivo measured with the comet assay.
To check the possibilities of the recently developed comet assay, to be used in mechanistic studies in Drosophila melanogaster, neuroblast cells of third instar larvae are used to analyse in vivo, the effect of two repair deficient mutations: mus201, deficient on nucleotide excision repair, and mus308, deficient in a mechanism of damage bypass, on the genotoxicity of methyl methanesulphonate (MMS), ethyl methanesulphonate (EMS) and N-ethyl-N-nitrosourea (ENU). The obtained results reveal: (1) MMS-induced breaks are most probably consequence of N-alkylation damage mediated abasic (AP) site breakage; (2) MMS and at least part of the EMS induced damage leading to DNA strand breaks are efficiently repaired by the nucleotide excision repair mechanism; (3) ENU and part of EMS induced damage need a functional Mus308 protein to be processed, otherwise they can lead to DNA strand breaks. In addition, the results of this work confirm the validity of neuroblast cells to conduct the comet assay, and the usefulness of this assay in in vivo mechanistic studies related to DNA repair in D. melanogaster.
Bilbao
Cristina
C
Departamento de Biología, Funcional e Instituto Universitario de Oncología Area de Genética, University of Oviedo, C/Julián Clavería s/n, 33006 Oviedo, Spain.
Ferreiro
José A
JA
Comendador
Miguel A
MA
Sierra
L María
LM
D000818:Animals; D020552:Comet Assay; D004249:DNA Damage; D004256:DNA Polymerase I / Q000235:genetics*; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase; D029721:Drosophila Proteins; D004331:Drosophila melanogaster; D004720:Endonucleases; D005020:Ethyl Methanesulfonate / Q000633:toxicity; D005038:Ethylnitrosourea / Q000633:toxicity; D006863:Hydrogen-Ion Concentration; D008741:Methyl Methanesulfonate / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D009687:Nuclear Proteins; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; D000097462:DNA Polymerase theta
D004256:DNA Polymerase I; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins; D004259:DNA-Directed DNA Polymerase; D029721:Drosophila Proteins; D004720:Endonucleases; D005020:Ethyl Methanesulfonate; D005038:Ethylnitrosourea; D008741:Methyl Methanesulfonate; D009153:Mutagens; D009687:Nuclear Proteins; D014157:Transcription Factors; D000099250:DNA Excision Repair Protein ERCC-5; C101782:DNApol-theta protein, Drosophila; D000097462:DNA Polymerase theta