Stressor: 127
Title
Stressor Overview
AOPs Including This Stressor
| AOP Name | Evidence |
|---|---|
| Chemical binding to tubulin in oocytes leading to aneuploid offspring | High |
Events Including This Stressor
| Event Name |
|---|
| Binding, Tubulin |
| Disorganization, Spindle |
| Altered, Meiotic chromosome dynamics |
| Altered, Chromosome number |
Chemical Table
| User term | DTXID | Preferred name | Casrn | jchem_inchi_key | indigo_inchi_key |
|---|---|---|---|---|---|
| Nocodazole | DTXSID9031800 | Nocodazole | 31430-18-9 | KYRVNWMVYQXFEU-UHFFFAOYSA-N | KYRVNWMVYQXFEU-UHFFFAOYSA-N |
AOP Evidence
Chemical binding to tubulin in oocytes leading to aneuploid offspring
Sun et al (2005) Hyperhaploidy is significantly increased at 70 mg/kg. The percentages of hyperhaploid oocytes were 0.0 (0/230), 0.0 (0/194) and 7.3 (8/110) for controls, 35 and 70 mg/kg, respectively. The lowest effective dose roughly corresponds to an in vitro concentration of 230 µM, much higher than active concentrations on cultured oocytes. Poor water solubility and limited bioavailability of nocodazole after i.p. treatment likely account for this difference.
Event Evidence
Binding, Tubulin
There is no evidence text for this event.
Disorganization, Spindle
In vitro expsoure of oocytes to 20 microgram/mL (67 microM) Nocodazole causes a gradual disassembly of the spindle , which is completed within 15 minutes (Xu et al 2002)
Altered, Meiotic chromosome dynamics
All tested concentrations induce spindle abnormalities in vitro. The lowest effective concentration for chromosome congression defects is 40 nM. The dose-response relationship are congruent with the proposed AOP (Shen et al 2005)
Altered, Chromosome number
In vitro expsoure to nocodazole for one hour during the first meiotic spindel formation induces a statistically significant increase in hyperploid mouse oocytes (Eichenlaub-Ritter and Boll, 1989). Subsequently, a dose-dependent increase in hyperhaploidy oocytes was found (Shen et al 2005); The lowest effective concentration for aneuploidy induction in metaphase II is 40 nM. This paper provides evidence of aneuploid linked to evidence of spindle and chromosome congression defects with a dose response relationship. The study of Sun et al (2005) confirmed the dose-dependent increase in hyperhaploid oocytes and showed that oocytes enclosed in their follicle appear more sensitive than denude oocytes to the aneugenic activity of nocodazole
In vivo, administration of 70 mg/kg nocodazole at the time of the induction of ovulation significantly increased hyperhaploid oocytes while a dose of 35 mg/kg did not (Sun et al 2005)