Cl. Doepker et al., STRUCTURAL AND NUMERICAL CHROMOSOMAL-ABERRATIONS IN A METABOLICALLY COMPETENT HUMAN LYMPHOBLAST CELL-LINE (MCL-5), Mutagenesis, 13(3), 1998, pp. 275-280
MCL-5 cells are Epstein Barr virus-transformed human lymphoblasts whic
h have been genetically engineered for use in mutagenicity testing. We
have examined the modal chromosome number, karyotype and spontaneous
micronucleus (MN) and sister chromatid exchange (SCE) frequencies of t
he cell line. Replicate experiments were conducted on two different sh
ipments purchased from Gentest Corp. Although the modal chromosome num
ber was 48 (range 40-54, n = 400 metaphases) for both cell shipments,
the second stock showed greater variation in chromosome number than th
e first. a total of 60 G-banded metaphase cells was analyzed and seven
karyotypes were prepared. Consistent structural abnormalities (transl
ocations, deletions and isochromosomes) were found involving the X chr
omosome and seven autosomes (1-3, 5, 6, 9 and 11), The karyotype typic
al of this cell line was: 48,der(X)t(X;?)(p22.3;?) Y,t(1;2)(q23;p23),d
el(3)(q12q12),+(3q),t(5;6) (q31;p23), +i(9p),der(11)t(11;13)(q23;q12).
The mean MN frequency was 41.8 MN/1000 binucleate cells (n = 5000), W
hen compared with our historical controls for primary lymphocyte cultu
res this number (41.8) is significantly (8.4-fold) higher, The mean SC
E frequency was 7.3 per metaphase (n = 100). We observed a hyperdiploi
d chromosome number of 48 in the majority of metaphase spreads, indica
ting a significant deviation from the normal diploid number characteri
stic of the parent cells (RPMI 1788) established in 1969. The variatio
n ire chromosome number distribution observed between shipments sugges
ts the potential for further changes, The elevated MN frequency sugges
ts that evaluating mutagenicity using this cytogenetic end-point may r
equire excessive dosing to produce a significant response over backgro
und. We conclude that careful interpretation of cytogenetic end-points
is necessary when using MCL-5 cells in the light of the possibility o
f clonal evolution presented here.