In vivo and in vitro cytogenetic effects of the anti-tumor agent amsacrina (AMSA).
The genotoxic effect of AMSA, an anti-tumor agent, was evaluated using the micronucleus and anaphase-telophase tests. The doses assayed by the in vivo micronucleus test were 1.5, 3 and 6 mg/kg: they are within the range of those used in clinical trials. A significant increase of micronucleated cells (P less than 0.01) was observed in the three assayed doses, with a linear dose response (r 0.98). In the in vitro test, 3 drug concentrations, i.e. 10, 1 and 0.1 microgram/ml, were analyzed with the 2 higher doses. AMSA showed a marked inhibition of cellular replication, but with 0.1 microgram/ml it was possible to determine an increase (P less than 0.01) in aberrations in anaphase-telophase cells. Both studies clearly demonstrate the clastogenic effect of the drug, which should be taken into account when considering its carcinogenic risk.
D000609:Aminoacridines / Q000633:toxicity*; D000677:Amsacrine; D000705:Anaphase / Q000187:drug effects; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects*; D002478:Cells, Cultured; D006224:Cricetinae; D005260:Female; D008297:Male; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D009152:Mutagenicity Tests; D010053:Ovary; D013692:Telophase / Q000187:drug effects
D000609:Aminoacridines; D000677:Amsacrine