title: Mutagenic and recombinagenic effects of lamivudine and stavudine antiretrovirals in somatic cells of Drosophila melanogaster.
abstract: Lamivudine (3TC) and stavudine (d4T) are nucleoside analogue reverse transcriptase inhibitors employed in antiretroviral therapies. The mutational and recombinational potential as well as the total genetic toxicity was determined for both compounds at concentrations allowing at least 30% survival using the standard version of wing SMART assay. The standardized clone induction frequency per mg/ml for mwh/flr(3) genotype were approximately 2 and approximately 33 mutant clones/10(5) cells/(mg/ml) for d4T and 3TC, respectively. Comparing these results with those obtained in the mwh/TM3 genotype, it was possible to quantify the recombinagenic action of each drug. Approximately 86% of the mutant clones induced by 3TC and approximately 76% of the d4T induced clones were related to their mitotic recombination action. Our results indicate that both 3TC and d4T have high recombinagenic potential, and suggest that exposure to the drugs could cause genomic instability and loss of heterozygosity. This may be due to the fact that these genetic alterations play a primary role in carcinogenesis, and are also involved in secondary and subsequent steps of carcinogenesis by which recessive oncogenic mutations are revealed.
authors.affiliation: Laboratório de Genética Toxicológica, Departamento de Bioquímica e Biologia Molecular, Instituto de Ciências Biológicas 2, Campus Samambaia, Universidade Federal de Goiás, Caixa Postal 131, CEP 74001-970, Goiânia, GO, Brazil.
authors.forename: Leonardo Pereira
authors.initials: LP
authors.lastname: Franchi
authors.forename: Nádia Helena Garofo Rodrigues
authors.initials: NH
authors.lastname: Pentiado
authors.forename: Renata do Nascimento
authors.initials: Rdo N
authors.lastname: Silva
authors.forename: Nilza Nascimento
authors.initials: NN
authors.lastname: Guimarães
authors.forename: Rosália Santos Amorim
authors.initials: RS
authors.lastname: Jesuino
authors.forename: Heloísa Helena Rodrigues
authors.initials: HH
authors.lastname: de Andrade
authors.forename: Maurício
authors.initials: M
authors.lastname: Lehmann
authors.forename: Kênya Silva
authors.initials: KS
authors.lastname: Cunha
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics; D019259:Lamivudine / Q000633:toxicity*; D009153:Mutagens / Q000633:toxicity*; D011995:Recombination, Genetic / Q000187:drug effects*; D018894:Reverse Transcriptase Inhibitors / Q000633:toxicity*; D018119:Stavudine / Q000633:toxicity*
chemical_list: D009153:Mutagens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D018119:Stavudine