Stressor: 127

Title

To create a new stressor, from the Listing Stressors page at https://aopwiki.org/stressors click ‘New stressor.’ This will bring you to a page entitled “New Stressor” where a stressor title can be entered. Click ‘Create stressor’ to create a new Stressor page listing the stressor title at the top. More help

Nocodazole

Stressor Overview

The stressor field is a structured data field that can be used to annotate an AOP with standardised terms identifying stressors known to trigger the MIE/AOP. Most often these are chemical names selected from established chemical ontologies. However, depending on the information available, this could also refer to chemical categories (i.e., groups of chemicals with defined structural features known to trigger the MIE). It can also include non-chemical stressors such as genetic or environmental factors. More help

AOPs Including This Stressor

This table is automatically generated and lists the AOPs associated with this Stressor. More help

AOP Name	Evidence
Chemical binding to tubulin in oocytes leading to aneuploid offspring	High

Events Including This Stressor

This table is automatically generated and lists the Key Events associated with this Stressor. More help

Event Name
Binding, Tubulin
Disorganization, Spindle
Altered, Meiotic chromosome dynamics
Altered, Chromosome number

Chemical Table

The Chemical Table lists chemicals associated with a stressor. This table contains information about the User’s term for a chemical, the DTXID, Preferred name, CAS number, JChem InChIKey, and Indigo InChIKey.To add a chemical associated with a particular stressor, next to the Chemical Table click ‘Add chemical.’ This will redirect you to a page entitled “New Stressor Chemical.’ The dialog box can be used to search for chemical by name, CAS number, JChem InChIKey, and Indigo InChIKey. Searching by these fields will bring forward a drop down list of existing stressor chemicals formatted as Preferred name, “CAS- preferred name,” “JChem InChIKey – preferred name,” or “Indigo InChIKey- preferred name,” depending on by which field you perform the search. It may take several moments for the drop down list to display. Select an entity from the drop down list and click ‘Add chemical.’ This will return you to the Stressor Page, where the new record should be in the ‘Chemical Table’ on the page.To remove a chemical associated with a particular stressor, in the Chemical Table next to the chemical you wish to delete, click ‘Remove’ and then click 'OK.' The chemical should no longer be visible in the Chemical table. More help

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

This table is automatically generated and includes the AOPs with this associated stressor as well as the evidence term and evidence text from this AOP Stressor. More help

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

This table is automatically generated and includes the Events with this associated stressor as well as the evidence text from this Event Stressor. More help

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

Text sections under this subheading include the Chemical/Category Description and Characterization of Exposure. More help

Chemical/Category Description

To edit the Chemical/Category Description” section, on a KER page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.” Scroll down to the “Chemical/Category Description” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page. The new text should appear under the “Chemical/Category Description” section on the page. More help

Characterization of Exposure

To edit the “Characterization of Exposure” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.” Scroll down to the “Characterization of Exposure” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page. The new text should appear under the “Characterization of Exposure” section on the page. More help

References

List of the literature that was cited for this Stressor description. Ideally, the list of references, should conform, to the extent possible, with the OECD Style Guide (https://www.oecd.org/about/publishing/OECD-Style-Guide-Third-Edition.pdf) (OECD, 2015).To edit the “References” section, on a Stressor page, in the upper right hand menu, click ‘Edit.’ This brings you to a page entitled, “Editing Stressor.” Scroll down to the “References” section, where a text entry box allows you to submit text. Click ‘Update’ to save your changes and return to the Stressor page. The new text should appear under the “References” section on the page. More help