API

Stressor: 127

Title

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Nocodazole

Stressor Overview

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AOPs Including This Stressor

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Events Including This Stressor

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Chemical Table

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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

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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

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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)




Stressor Info

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Chemical/Category Description

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Characterization of Exposure

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References

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