Analysis of historical negative control group data from the in vitro micronucleus assay using human lymphocytes

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis Vol. 837; pp. 52 - 59
• Main Authors: Lovell, David P., Fellow, Mick, Elhajouji, Azeddine, Farabaugh, Christopher S., Gilby, Ben G., Hashimoto, Kiyohiro, Li, Yan, Roy, Shambhu, Schuler, Maik, Whitwell, James, Tanir, Jennifer Y.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2019
• Subjects: Historical negative control data; Human lymphocytes; In vitro micronucleus assay; Quality control statistics; Human lymphocytes; In vitro micronucleus assay; Historical negative control data; Quality control statistics
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2018.08.009

•Laboratory-specific historical negative control data are important for assessing data quality and for interpretation.•Historical control data from eight laboratories from in vitro micronucleus assays using human lymphocytes were analyzed.•Mean incidences amongst laboratories ranged from 2.2 to 15.9 micronucleated cells/1000 cells. A database of the micronuclei counts was built up for historical negative control data from human lymphocyte in vitro micronuclei tests (MnVit) carried out in 8 laboratories with experience of the method. The mean incidence of micronucleated cells (mnt)/1000 cells ranged from 2.2/1000 to 15.9/1000. There were no large differences in incidence between the presence or absence of S9 mix or between different treatment lengths. There was also little evidence that different solvents affected the numbers of micronuclei appreciably. A number of laboratories did show significant inter-experiment variability, indicating that there remained unidentified factors affecting frequencies. Donor variance may be one such factor. Inter-individual variability may explain some of these differences. The approximate 7.5-fold difference in mnt/1000 scores in a relatively small group of experienced laboratories illustrates the potential complications that can arise if a metric like a fold increase was considered the only biologically important finding. Although there is inherent variability between experiments, it was evident that within a laboratory the overall laboratory mean remains constant over time. It is believed that these findings will provide help to laboratories conducting studies using human lymphocytes in the MnVit and to those involved in the assessment of MnVit results.