A Chinese hamster ovary cell mutant (EM-C11) with sensitivity to simple alkylating agents and a very high level of sister chromatid exchanges.
We have isolated a Chinese hamster ovary cell mutant hypersensitive to monofunctional alkylating agents. The mutant, designed as EM-C11, showed hypersensitivity to ethyl methanesulfonate (EMS), methyl methanesulfonate and ethylnitrosourea (8-, 7- and 2-fold, respectively, based on D10 values). About 2-fold increased sensitivity towards 4-nitroquinoline-1-oxide and only slightly increased sensitivity to X-rays (1.4-fold) and mitomycin C treatment (1.6-fold) were found in this mutant. EM-C11 was not hypersensitive to UV irradiation nor to adriamycin. The EM-C11 cells showed approximately 10-fold higher level of spontaneous sister chromatid exchange. The level of spontaneous chromosomal aberrations was 2- to 3-fold higher, but the frequency of EMS-induced chromosomal aberrations was approximately 10-fold higher in the mutant cells, in agreement with the increased sensitivity to killing. As measured by alkaline elution, EM-C11 cells showed a defect in the rejoining of single-strand DNA breaks after exposure to X-rays and even more so after the EMS treatment. Genetic analysis revealed that the EM-C11 mutant belongs to the same complementation group as the EM9 mutant described earlier. The XRCC1 gene which complements the defect in EM9 also complements the defect in EM-C11, confirming that these two independently isolated mutants are defective in the same gene.
Zdzienicka
M Z
MZ
MGC-Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, Sylvius Laboratory, The Netherlands.
van der Schans
G P
GP
Natarajan
A T
AT
Thompson
L H
LH
Neuteboom
I
I
Simons
J W
JW
D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D016466:CHO Cells; D002470:Cell Survival / Q000187:drug effects; D002869:Chromosome Aberrations / Q000235:genetics; D006224:Cricetinae; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D005260:Female; D005816:Genetic Complementation Test; D009154:Mutation / Q000235:genetics; D010053:Ovary / Q000187:drug effects*; D012854:Sister Chromatid Exchange / Q000235:genetics*
D000477:Alkylating Agents