In Vitro Mammalian Cell Micronucleus Test (OECD 487)
The In Vitro Micronucleus Test (MNT) is used to detect chemicals which induce the formation of small membrane-bound DNA fragments (micronuclei) in the cytoplasm of interphase cells.
Chromosomal damage is detected by the presence of micronuclei in the cytoplasm of interphase cells that originate from acentric fragments, or whole chromosomes that failed to segregate correctly during anaphase. This means the micronucleus test is sensitive to both clastogenic and aneugenic mechanisms of genotoxicity.
This cytogenetic test forms part of the standard test battery for genotoxicity as prescribed by the International Conference on Harmonization (ICH S2 (R1) and is also designed to meet the requirements of the current international guidelines issued by the Organization for Economic Cooperation and Development (OECD; Test Guideline 487).
The assay can be performed at Gentronix to a GLP standard as part of pre-clinical requirements, but modified versions of the MNT assay are available for screening purposes with reduced compound obligations whilst still fulfilling guideline criteria.
Gentronix primarily offers MNT in p53 competent TK6 Human Lymphoblastoid cells and Primary Human Lymphocytes. Recent publications have shown that choice of cell line can reduce the number of misleading ‘false’ positives in the in vitro MNT compared with in vivo genotoxicity data, with p53 deficiency in rodent cell lines being a key factor in susceptibility to cytotoxicity and micronucleus induction. Other cell types may be available for testing upon request and customers can contact Gentronix for further information.
When requesting a GLP study, the sponsor will typically provide test item characterisation and formulation information, and analytical methods for formulation analysis.
A draft study plan is prepared for review by the sponsor, Gentronix, and QA group. Once this is approved and the test items supplied, the study can begin.
If formulation analysis is required, this is carried out immediately after dosing.
The sponsor is notified of the results of the study.
A draft report is prepared and reviewed by the sponsor, Gentronix and the QA group. Once approved, a QA statement is added before the final report is issued.