Evidence that DNA double-strand breaks initiate the phenotype of delayed reproductive death in Chinese hamster ovary cells.
A persistently reduced cloning efficiency occurs in many of the cloned progeny of Chinese hamster ovary (CHO) cells surviving X irradiation, a stable phenotype we have previously termed delayed reproductive death (Int. J. Radiat. Biol. 60, 483-496, 1991). We now report that this phenotype is also induced by the alkylating agent ethyl methanesulfonate (EMS), but not by irradiation with ultraviolet light. The restriction endonuclease HinfI, which binds at G [symbol: see text] ANTC DNA sequences and generates cohesive-end double-strand breaks, was also efficient in inducing delayed reproductive death. On the other hand, an X-ray-sensitive CHO mutant, xrs-5, which is defective in the repair of DNA double-strand breaks, did not show this phenotype following X irradiation. These results suggest that DNA double-strand breaks, as well as the endogenous repair processes for these breaks, are associated with the induction of the delayed reproductive death phenotype in CHO cells. The possible mechanism for the induction of delayed reproductive death by EMS is discussed.
Chang
W P
WP
Laboratory of Radiobiology, Harvard University School of Public Health, Boston, Massachusetts 02115.
Little
J B
JB
D000818:Animals; D016466:CHO Cells; D016923:Cell Death / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D006224:Cricetinae; D004247:DNA / Q000187:drug effects / Q000528:radiation effects*; D004249:DNA Damage; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D010641:Phenotype; D013997:Time Factors
D004247:DNA; D005020:Ethyl Methanesulfonate