Comparative genotoxic effect of vincristine, vinblastine, and vinorelbine in somatic cells of Drosophila melanogaster.
In this study, the vinca alkaloids vincristine (VCR), vinblastine (VBL) and vinorelbine (VNR) were investigated for genotoxicity in the wing Somatic Mutation and Recombination Test (SMART) of Drosophila. Our in vivo experiments demonstrated that all drugs assessed induced genetic toxicity, causing increments in the incidence of mutational events, as well as in somatic recombination. Another point to be considered is the fact that VNR was able to induce, respectively, approximately 13.0 and 1.7 times more mutant clones per millimolar exposure unit as their analogues VCR and VBL. The replacement of a CH(3) attached to vindoline group in VBL by a CHO in VCR seems to be responsible for the approximately seven times higher potency of the former. In contrast, the structural modifications on VNR's catharantine group could be related to its higher genotoxic potency, as well as its similar mutagenic and recombinagenic action.
Tiburi
Marcelo
M
South-American Office for Anticancer Drug Development (SOAD), Universidade Luterana do Brasil, Canoas, RS, Brazil.
Reguly
Maria Luiza
ML
Schwartsmann
Gilberto
G
Cunha
Kênya Silva
KS
Lehmann
Maurício
M
Rodrigues de Andrade
Heloísa Helena
HH
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D005260:Female; D005854:Germ Cells / Q000502:physiology; D007814:Larva; D008297:Male; D015394:Molecular Structure; D009152:Mutagenicity Tests; D011995:Recombination, Genetic; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000633:toxicity*; D014750:Vincristine / Q000633:toxicity*; D000077235:Vinorelbine; D014921:Wings, Animal / Q000502:physiology*
D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D014747:Vinblastine; D000077235:Vinorelbine