Cytotoxic and genotoxic actions of Casiopeina III-Ea (Cas III-Ea) in somatic and germ cells of Drosophila melanogaster

J Toxicol Environ Health A. 2017;80(6):365-373. doi: 10.1080/15287394.2017.1326072. Epub 2017 Jun 23.

Abstract

Casiopeinas® are a group of newly synthesized drugs designed to treat cancer. These copper (Cu) complexes exhibit cytostatic, cytotoxic, genotoxic, and antineoplastic activities through different mechanisms of action. To evaluate the influence of these compounds, some in vivo studies were performed using predominantly somatic cells. The aim of the present study was to examine the cytotoxic and genotoxic actions of Casiopeina III-Ea (Cas III-Ea) in somatic as well as germ cells of Drosophila melanogaster. For cytotoxicity, the productivity and some morphometric parameters were measured and genotoxicity was assessed by means of the somatic mutation and recombination test assay in the wing. For this purpose, second-instar larvae of the Canton-S strain were treated with different concentrations of Cas III-Ea. The emerged adults were weighed, the area of the wings determined, and the number of trichomes of the region C' counted. The productivity of treated males was measured by a brood method to monitor the influence of Cas III-Ea on spermatozoa, meiotic stage cells, and spermatogonia. For genotoxicity, mwh + /+ flr3 larvae 48 hr age were chronically treated within the same concentration range. Results indicated that Cas III-Ea at all concentrations tested significantly increased the productivity per couple in Brood III (spermatids) while at 1 mM a marked elevation was noted in the three broods tested. In contrast, the weight and size of individuals as well as the size and number of cells in the wing were decreased significantly. Data suggest that Cas III-Ea is a weak genotoxic but selective mutagen. Failure to obtain a dose-related genotoxic response suggests that one of the preferred mechanisms of action of Cas III-Ea is to induce apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Coordination Complexes / toxicity*
  • Drosophila melanogaster / drug effects
  • Female
  • Germ Cells / drug effects
  • Male
  • Mutagenicity Tests
  • Phenanthrolines / toxicity*
  • Wings, Animal / drug effects

Substances

  • (Cu(4,7-dimethyl-1,10-phenanthroline)(acetylacetonato)(H2O))NO3
  • Antineoplastic Agents
  • Coordination Complexes
  • Phenanthrolines