P. Telleman et al., A NEW COMPLEMENTATION GROUP OF MITOMYCIN C-HYPERSENSITIVE CHINESE-HAMSTER CELL MUTANTS THAT CLOSELY RESEMBLES THE PHENOTYPE OF FANCONI-ANEMIA CELLS, Cancer research, 55(15), 1995, pp. 3412-3416
Three Mitomycin C (MMC)-hypersensitive mutants (CL-V1B, CL-V5B, and CL
-V101B) were isolated from Chinese hamster V79B cells by the replica p
lating technique. In comparison to the parental cell Line, CL-V1B, CL-
V5B, and CL-V101B show about a 22-, 32-, and 13-fold increased sensiti
vity to MMC, respectively (judged by the D-10). These mutants are also
sensitive to other DNA cross-linking agents, such as 1,2,3,4-diepoxyb
utane (9-, 19-, and 12-fold, respectively) and cis-diamminedichloropla
tinum(II) (17-, 12-, and 6-fold, respectively). CL-V5B and CL-V101B di
splay an exclusive sensitivity to DNA cross-linking agents, whereas CL
-V1B also shows an increased sensitivity to monofunctional alkylating
agents, such as methyl methanesulfonate (3-fold) and ethyl methanesulf
onate (2-fold), and UV254nm (2-fold). Approximately 2-3-fold higher le
vels of spontaneous chromosomal aberrations are found in these three m
utants in comparison to wild-type V79B cells. At a MMC survival level
of 80%, CL-V5B demonstrates a 16-fold higher level of MMC-induced chro
mosomal damage than V79B. Despite phenotypical heterogeneity within th
is group of mutants, hybrid clones derived after fusion remained MMC s
ensitive, indicating that these mutants belong to the same complementa
tion group. To determine whether the mutants represent a new complemen
tation group among other Chinese hamster cell mutants that also displa
y hypersensitivity to MMC, CL-V1B cells were fused with mutants repres
enting different complementation groups i.e., irs1, irs3, irs1SF, UV20
, UV41, V-H4, and V-C8 cells. In all cases, the derived hybrids regain
ed MMC sensitivity similar to wild-type cells, indicating that the CL-
V1B mutant represents a new complementation group. The phenotype of CL
-V1B, CL-V5B, and CL-V101B cells closely resembles the phenotype of Fa
nconi anemia cells, suggesting that these hamster mutants could be def
ective in a gene that is involved in this disorder.