Kl. Radack et al., SOURCES OF VARIABILITY IN THE HUMAN LYMPHOCYTE MICRONUCLEUS ASSAY - APOPULATION-BASED STUDY, Environmental and molecular mutagenesis, 26(1), 1995, pp. 26-36
The cytokinesis block method was used to examine the intraclass correl
ation coefficient of the human lymphocyte micronucleus assay, sources
of variability, and practical issues regarding he number of samples pe
r subject. Twenty samples of 100 binucleate cells from a single phlebo
tomy per subject were analyzed (n = 112), using methods to evaluate va
riance components. The results showed marked intraindividual (sampling
error) variation greeter than interindividual variation, and no betwe
en-group contribution to the total variance. The intraclass correlatio
n was 41.6%, indicating that slightly greater than half of the total v
ariation in micronucleus outcomes was due to error variance (i.e., 58.
4%). After adjusting for age, the intraclass correlation coefficient d
ecreased trivially from 41.6% to 39.8%. There was a strong differentia
l gender effect, favoring a greater micronuclei frequency in women. In
conclusion, the data suggest that most of the variability in our data
set for the micronucleus assay was due to sampling error; a strong di
fferential gender effect favoring females was also verified. Equally i
mportant, in terms of practical applications, our analysis of the appr
opriate number of samples per subject revealed that scoring greater th
an 1,000 cells (10 determinations per subject) yielded no substantial
improvement in statistical sensitivity, compared to the traditional 20
determinations. We suggest that more attention should be directed tow
ard improving the assay's utility, while reducing sampling error. (C)
1995 Wiley-Liss, Inc.