Ataxia-telangiectasia-like Chinese hamster V79 cell mutants with radioresistant DNA synthesis, chromosomal instability, and normal DNA strand break repair.
We have isolated three radiosensitive mutants (V-C4, V-E5, and V-G8) of the Chinese hamster V79 cell line which also show increased sensitivities to killing by bleomycin (approximately 2-5-fold) and ethyl methanesulfonate (approximately 2-fold). Genetic complementation analysis indicates that all three mutants belong to one complementation group. The mutants show a radioresistant DNA synthesis following X-ray irradiation when compared to wild-type V79 cells. Both the level and the rate of repair of DNA single- and double-strand breaks measured by DNA elution were similar to those observed in wild-type V79 cells. The level of spontaneously occurring chromosome aberrations in two of these mutants differs severalfold from the level observed in wild-type V-79 cells and in V-G8, to approximately 2- and 6-fold increase in V-E5 and V-C4, respectively. X-irradiation of the mutants resulted in consistently 3-4-fold higher levels of chromatid gaps, breaks, and exchanges than observed in wild-type V79 cells. In addition, G1 irradiation of the mutant cells yielded both chromosome and chromatid types of aberrations. The level and pattern of chromosomal aberrations induced by X-rays in V-C4, V-E5, and V-G8 are similar to those observed in ataxia-telangiectasia cells. These results indicate that our mutants represent the first rodent cell mutants which show phenotypic characteristics strongly resembling those in cells from ataxia-telangiectasia patients.
Zdzienicka
M Z
MZ
Department of Radiation Genetics and Chemical Mutagenesis, State University of Leiden, The Netherlands.
Jaspers
N G
NG
van der Schans
G P
GP
Natarajan
A T
AT
Simons
J W
JW
D000818:Animals; D001260:Ataxia Telangiectasia / Q000235:genetics*; D001761:Bleomycin / Q000494:pharmacology; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000096:biosynthesis*; D004249:DNA Damage; D004260:DNA Repair; D005816:Genetic Complementation Test; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D011836:Radiation Tolerance
D001761:Bleomycin; D004247:DNA; D008741:Methyl Methanesulfonate