Detection of mitotic recombination and sex chromosome loss induced by adriamycin, chlorambucil, demecolcine, paclitaxel and vinblastine in somatic cells of Drosophila melanogaster in vivo.
The conventional w/w+ eye assay in Drosophila has been used for the last 10 years for genotoxic evaluation of a broad number of chemicals with different mechanisms of action. Although chemicals that induce genotoxic effects by mechanisms other than covalent binding to DNA are difficult to detect. The aim of this study was the parallel detection of both mitotic recombination and X chromosome loss induced by five chemical compounds used worldwide as antineoplastic drugs using the w/w+ somatic assay in Drosophila melanogaster. The compounds tested were the intercalating agent adriamycin (AD), the alkylating compound chlorambucil (CAB) and the spindle poisons demecolcine (DEM), paclitaxel (taxol, TX) and vinblastine (VBL). We used a cross between heterozygous females with a rod-X and a ring-X chromosome mated with ywf males. All four genotypes in the next generation are heterozygous or hemizygous for the w+ reporter gene and were inspected for the occurrence of white clones in their compound eyes. We found differences in the induction of mitotic recombination when compared with chromosome loss. Genotoxic profiles obtained for the antineoplastic drugs studied indicate direct and indirect effects. While AD seems to be clastogenic due to its induction of X chromosome loss in XrX females; DEM, CAB and TX produced both structural chromosome aberrations through clastogenic activities and mitotic recombination through DNA interactions; the cytotoxic VBL induced rX loss only in XrY and intra-chromosomal recombination (XY) males, probably due to sister strand recombination, generating a w+w+ duplication and a w- deletion, forward mutations or small deletions at the white locus.
Rodríguez-Arnaiz
Rosario
R
Laboratorio de Genética, Facultad de Ciencias, UNAM, Coyoacán, 04510 México, DF México. rra@hp.fciencias.unam.mx
Sortibrán
América Castañeda
AC
Téllez
Guadalupe Ordaz
GO
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002699:Chlorambucil / Q000494:pharmacology; D003703:Demecolcine / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology; D011995:Recombination, Genetic / Q000187:drug effects*; D012730:Sex Chromosomes / Q000187:drug effects*; D014747:Vinblastine / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D002699:Chlorambucil; D014747:Vinblastine; D004317:Doxorubicin; D017239:Paclitaxel; D003703:Demecolcine