Premium
Comparative analysis of genetic toxicity of AZT and ddI antiretrovirals in somatic cells of Drosophila melanogaster
Author(s) -
Guimarães Nilza Nascimento,
de Castro Pereira Karla,
de Andrade Heloísa Helena Rodrigues,
Lehmann Maurício,
Silva Cunha Kênya
Publication year - 2008
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.20389
Subject(s) - mitotic crossover , didanosine , biology , zidovudine , homologous recombination , drosophila melanogaster , reverse transcriptase , mutation , virology , mutagen , point mutation , genetics , toxicity , nucleoside analogue , recombination , microbiology and biotechnology , virus , nucleoside , carcinogen , dna , chemistry , rna , viral disease , gene , organic chemistry
Antiretroviral therapies based on nucleoside reverse transcriptase inhibitors, like zidovudine (3′‐azido‐3′‐deoxythymidine; AZT) and didanosine (2′,3′‐dideoxyinosine; ddI), markedly reduce human immunodeficiency virus loads. The Somatic Mutation And Recombination Test in Drosophila melanogaster (wing SMART), in its standard version, was applied to compare AZT and ddI genetic toxicity expressed as point and chromosomal mutation as well as homologous mitotic recombination. The present findings provide evidence that the mechanistic basis underlying the genetic toxicity of these antiretrovirals is mainly related to mitotic recombination. However, a genotoxic pattern can correspondingly be discerned: AZT is able to induce recombination (∼85%) and mutation (∼15%), and ddI causes only homologous recombination (100%) in the wing SMART assay. Another point to be considered is the fact that ddI is 3.8 times less active to induce mutant clones per mg/ml unit as compared to AZT. The clinical significance of these observations has to be interpreted in the light of data obtained from long‐term toxicity in patients treated with the above mentioned agents. Environ. Mol. Mutagen., 2008. © 2008 Wiley‐Liss, Inc.