title: Comparative analysis of genetic toxicity of antiretroviral combinations in somatic cells of Drosophila melanogaster.
abstract: Nucleoside reverse-transcriptase inhibitor (NRTI) drugs are a major component of highly-active antiretroviral therapy (HAART). NRTI combinations have been demonstrated as producing a sustained reduction in plasma viremia with an increased CD4 count, thereby showing clear clinical benefits. Therefore, the secondary effects caused by the combination of two NRTIs, mainly those related to amplification of genotoxic effects, due to increased risk of DNA damage caused by these drugs, should be carefully examined. We employed the standard version of the wing SMART in Drosophila melanogaster to obtain more detailed knowledge about the genotoxic profile of NRTI combinations of AZT+ddI, AZT+3TC and AZT+d4T. Our results showed that all combinations increased the frequencies of induction of mutant spots. The combinations AZT+ddI and AZT+3TC were shown to induce recombination rates ranging from 86.38% to 98.36% while AZT+d4T showed a large discrepancy between recombination and mutation percentages. The combination index demonstrated that 3TC and d4T produced antagonism while ddI showed synergistic effects in combination with AZT.
authors.affiliation: Laboratório de Genética Toxicológica, Departamento de Bioquímica e Biologia Molecular, Instituto de Ciências Biológicas (ICB), Universidade Federal de Goiás (UFG), Goiânia, GO, Brazil.
authors.forename: N N
authors.initials: NN
authors.lastname: Guimarães
authors.forename: C J
authors.initials: CJ
authors.lastname: Silva
authors.forename: H H R
authors.initials: HH
authors.lastname: de Andrade
authors.forename: R R
authors.initials: RR
authors.lastname: Dihl
authors.forename: M
authors.initials: M
authors.lastname: Lehmann
authors.forename: K S
authors.initials: KS
authors.lastname: Cunha
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000009:adverse effects; D000998:Antiviral Agents / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D004249:DNA Damage / Q000187:drug effects*; D016049:Didanosine / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000378:metabolism; D004338:Drug Combinations; D005260:Female; D019259:Lamivudine / Q000009:adverse effects; D008297:Male; D008938:Mitosis; D009154:Mutation; D011994:Recombinant Proteins; D014921:Wings, Animal / Q000187:drug effects; D015215:Zidovudine / Q000009:adverse effects
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D004338:Drug Combinations; D011994:Recombinant Proteins; D019259:Lamivudine; D015215:Zidovudine; D016049:Didanosine