The genetic toxicity effects of lamivudine and stavudine antiretroviral agents.
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.
Guimarães
Nilza Nascimento
NN
Laboratório de Genética Toxicológica, Departamento de Bioquímica e Biologia Molecular (DBBM), Instituto de Ciências Biológicas (ICB), Universidade Federal de Goiás (UFG), Goiânia, GO, Brasil.
de Andrade
Heloísa Helena Rodrigues
HH
Lehmann
Maurício
M
Dihl
Rafael Rodrigues
RR
Cunha
Kênya Silva
KS
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
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D018119:Stavudine