Germ cells microsatellite instability. The effect of different mutagens in a mismatch repair mutant of Drosophila (spel1).
Mismatch repair (MMR) process confers a type of genomic stability that maintains stable single repeated sequences, hence a failure of this process could deviate in cancer development. A characteristic phenotype of MMR-deficient cells is microsatellite instability (MSI) that could be modulated by mutagenic agents. The induction of MSI by the mutagens, bleomycin (BLM), hydrogen peroxide (H(2)O(2)), 2-acetylaminofluorene (2-AAF) and ethidium bromide (EB) was evaluated in vivo, by using a Drosophila melanogaster-null mutant of the msh2 mismatch repair gene (spel1). Whereas in the germ cells of the spel1 strain, we found microsatellite mutations in the five repeated sequences studied in untreated individuals, no alterations were found in the MMR-proficient strain. On the other hand, the data obtained from the treatment experiments show that BLM and 2-AAF induced a slight mutagenic effect in the MMR-deficient background but not in the normal one. These results indicate that the use of the Drosophila spel1 mutant (MMR-deficient) could be of relevant importance to identify environmental factors involved in carcinogenesis processes through genomic instability.
López
A
A
Grup de Mutage'nesi, Unitat de Genètica, Departament de Gene'tica i de Microbiologia, Edifici Cn, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain.
Xamena
N
N
Marcos
R
R
Velázquez
A
A
D015073:2-Acetylaminofluorene / Q000633:toxicity; D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000633:toxicity; D020137:Base Pair Mismatch; D001761:Bleomycin / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D004260:DNA Repair; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D004996:Ethidium / Q000633:toxicity; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D008297:Male; D018895:Microsatellite Repeats; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D011994:Recombinant Proteins / Q000235:genetics* / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D002273:Carcinogens; D029721:Drosophila Proteins; D009153:Mutagens; D011994:Recombinant Proteins; C118784:spel1 protein, Drosophila; D001761:Bleomycin; D015073:2-Acetylaminofluorene; D006861:Hydrogen Peroxide; D004996:Ethidium