Meiotic arrest and aneuploidy induced by vinblastine in mouse oocytes.
Young superovulated female mice were injected i.p. with single doses of vinblastine sulfate just before the onset of the first meiotic division. Secondary oocytes, fixed one by one on a slide, were cytogenetically scored. Evidence of the meiotic arresting activity of vinblastine was produced by the observation of increasing frequencies of M1-arrested oocytes and by the presence of undegenerated chromosome sets of first polar bodies. When the first meiotic division could be undertaken chromosome malsegregation occurred with high frequency, both in terms of aneuploidy and polyploidy. M1-blocked and polyploid oocytes have been interpreted as the consequence of irreversible damage to the spindle induced by vinblastine through its binding on tubulin low-affinity sites; this reaction, in fact, causes microtubule crystallization. According to this mechanism, dose-effect relationships of both phenomena show a threshold at 0.45 mg/kg. On the other hand, the incidence of aneuploid oocytes is correlated with meiotic delay, as detected by the delayed degeneration of polar bodies, and increases linearly with dose. Both phenomena are, therefore, stochastic and can be referred to the binding of the chemical on tubulin high-affinity sites, which is known to cause tubulin depolymerization in a colchicine-like way.
Russo
A
A
Lab. Toxicology ENEA, Rome, Italy.
Pacchierotti
F
F
D000782:Aneuploidy; D000818:Animals; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008540:Meiosis / Q000187:drug effects*; D051379:Mice; D009865:Oocytes / Q000187:drug effects*; D009866:Oogenesis / Q000187:drug effects; D014747:Vinblastine / Q000494:pharmacology*
D014747:Vinblastine