title: The genetic toxicity effects of lamivudine and stavudine antiretroviral agents.
abstract: BACKGROUND
  The nucleoside reverse transcriptase inhibitors (NRTIs) are used in antiretroviral therapy worldwide for the treatment of HIV infections. These drugs act by blocking reverse transcriptase enzyme activity, causing pro-viral DNA chain termination. As a consequence, NRTIs could cause genomic instability and loss of heterozygosity.
  
  
  METHODS
  This review highlights the toxic and genotoxic effects of NRTIs, particularly lamivudine (3TC) and stavudine (d4T) analogues. In addition, a battery of short-term in vitro and in vivo systems are described to explain the potential genotoxic effects of these NRTIs as a single drug or a complexity of highly active antiretroviral therapy.
  
  
  RESULTS
  The readers will gain an understanding of a secondary effect that could be induced by 3TC and d4T treatments.
  
  
  CONCLUSIONS
  Considering that AIDS has become a chronic disease, more comprehensive toxic genetic studies are needed, with particular attention to the genetic alterations induced by NRTIs. These alterations play a primary role in carcinogenesis and are also involved in secondary and subsequent steps of carcinogenesis.
authors.affiliation: Laboratório de Genética Toxicológica, Departamento de Bioquímica e Biologia Molecular (DBBM), Instituto de Ciências Biológicas (ICB), Universidade Federal de Goiás (UFG), Goiânia, GO, Brasil.
authors.forename: Nilza Nascimento
authors.initials: NN
authors.lastname: Guimarães
authors.forename: Heloísa Helena Rodrigues
authors.initials: HH
authors.lastname: de Andrade
authors.forename: Maurício
authors.initials: M
authors.lastname: Lehmann
authors.forename: Rafael Rodrigues
authors.initials: RR
authors.lastname: Dihl
authors.forename: Kênya Silva
authors.initials: KS
authors.lastname: Cunha
mesh_terms: D000328:Adult; D000818:Animals; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000633:toxicity; D002648:Child; D002869:Chromosome Aberrations / Q000187:drug effects*; D002986:Clinical Trials as Topic; D006224:Cricetinae; D004331:Drosophila melanogaster / Q000187:drug effects / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D000882:Haplorhini; D006801:Humans; D019259:Lamivudine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000633:toxicity; D051379:Mice; D009152:Mutagenicity Tests; D009154:Mutation; D051381:Rats; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000633:toxicity; D018119:Stavudine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D018119:Stavudine