Kinetics of micronucleated polychromatic erythrocyte (MN-PCE) induction in vivo by aneuploidogens.
The aim of the present study was to make inferences about the cytotoxic and genotoxic action of the antineoplastic aneuploidogens, vinblastine and vincristine, by analyzing the kinetics of MN-PCE induction in mice in vivo. The kinetics of MN-PCE induction was assessed by taking blood samples from the tail, before the single i.p. injection of different doses of vinblastine or vincristine and every 8h after that. The analysis was done in groups consisting of three or four animals. The results indicate that both agents have similar kinetics of MN-PCE induction which differs from the kinetics previously obtained for colchicine in the following aspects: (i) vinblastine and vincristine cause a longer delay after exposure, (ii) they produce a higher maximal velocity of induction, and (iii) higher doses give rise to more than one peak in the curve of MN-PCE frequency versus time. The results of the present study indicate that the different mechanisms of action of vinca alkaloids and colchicine are reflected in their kinetics of MN-PCE induction, and that such mechanisms could also explain the differences in their efficiency. Vinca alkaloids seem to block the cell division immediately, but the cell appears to be capable of reverting the blockage during the period of time corresponding to the first division. Moreover, evidence was obtained indicating that high doses could induce a long lasting aneuploidogen effect, probably related to the accumulation of vinca alkaloids that are either free or associated to tubulin.
Morales-Ramírez
Pedro
P
Departamento de Biología, Instituto Nacional de Investigaciones Nucleares, Apartado Postal 18-1027, Mexico, D.F., Mexico. pmr@nuclear.inin.mx
Vallarino-Kelly
Teresita
T
Cruz-Vallejo
Virginia
V
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000139:chemically induced; D015162:Micronucleus Tests; D014747:Vinblastine / Q000494:pharmacology*; D014750:Vincristine / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D014750:Vincristine; D014747:Vinblastine