Altered metaphase chromosome structure in xrs-5 cells is not related to its radiation sensitivity or defective DNA break rejoining.
The chinese hamster ovary (CHO) cell line xrs-5 is a radiation-sensitive derivative of CHO-K1 cells. The xrs-5 cells have a defect in DNA double-strand break rejoining and show alterations in chromosome structure and nuclear morphology. The relationship between radiation sensitivity and metaphase chromosome morphology was examined in 12 'revertant' xrs-5 clones isolated following treatment with 5-azacytidine. nine of the clones were radioresistant while the other three retained xrs-5-like radiation sensitivity. Chromosome morphology reverted to CHO-K1-like characteristics in three of the radioresistant clones and one of the radiosensitive clones suggesting that the over-condensed metaphase chromosome morphology of xrs-5 cells does not underlie its radiation sensitivity. Radiation sensitivity did correlate with DNA double-strand break rejoining ability. The radioresistant clones showing the over-condensed xrs-5-like chromosome morphology were also slightly more sensitive to the topoisomerase II inhibitor etoposide (VP-16) than CHO-K1, suggesting that the over-condensed morphology might be due to alterations in the phosphorylation of chromatin proteins.
Schwartz
J L
JL
Center for Mechanistic Biology and Biotechnology, Argonne National Laboratory, IL 60439-4833, USA.
Brinkman
W J
WJ
Kasten
L
L
Miller
D W
DW
Moan
E I
EI
Murphy
Y T
YT
Stella
D
D
Sedita
B A
BA
D000818:Animals; D034961:Antigens, Nuclear; D001374:Azacitidine / Q000494:pharmacology; D016466:CHO Cells; D002843:Chromatin / Q000378:metabolism; D002875:Chromosomes / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D006224:Cricetinae; D004265:DNA Helicases; D004260:DNA Repair / Q000235:genetics*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics; D005720:Gamma Rays; D000072200:Ku Autoantigen; D008677:Metaphase; D009687:Nuclear Proteins / Q000235:genetics; D010766:Phosphorylation; D011836:Radiation Tolerance / Q000235:genetics*
D034961:Antigens, Nuclear; D002843:Chromatin; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; D000072200:Ku Autoantigen; D004250:DNA Topoisomerases, Type II; D001374:Azacitidine