Mutagenic and recombinagenic effects of lamivudine and stavudine antiretrovirals in somatic cells of Drosophila melanogaster.
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.
Franchi
Leonardo Pereira
LP
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.
Pentiado
Nádia Helena Garofo Rodrigues
NH
Silva
Renata do Nascimento
Rdo N
Guimarães
Nilza Nascimento
NN
Jesuino
Rosália Santos Amorim
RS
de Andrade
Heloísa Helena Rodrigues
HH
Lehmann
Maurício
M
Cunha
Kênya Silva
KS
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*
D009153:Mutagens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D018119:Stavudine