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Deficiency in DNA repair in mouse lymphoma strain L5178Y-S

Journal Article · · Proc. Natl. Acad. Sci. U.S.A.; (United States)
The production and repair of radiation-induced DNA damage were measured by filter elution in strains of mouse lymphoma L5178Y cells differing in their sensitivity to ionizing radiation. The induction of radiation-induced damage, as measured by filter elution at pH 12.1, 9.6, and 7.2, was similar in the resistant strain LY-R and the sensitive strain LY-S. The repair of single-strand breaks and alkali-labile sites, as measured by filter elution at pH 12.1 at various times after irradiation, was somewhat slower in strain LY-S than in strain LR-R. However, when filter elution was performed at either pH 9.6 or pH 7.2, the repair of x-radiation-induced damage was much less extensive in strain LY-S than in strain LY-R. The authors have assumed that the extent of filter elution at pH 9.6 is a measure of the occurrence of frank double-strand breaks as well as closely opposing single-strand breaks and pH 9.6-labile sites (and combinations thereof), and that the extent of elution at pH 7.2 is a measure of the occurrence of frank double-strand breaks alone. If these assumptions are correct, the results suggest that the sensitivity of strain LY-S to the cytotoxic effects of ionizing radiation is caused by a deficiency in the ability of this strain to repair frank double-strand breaks and pH 9.6-labile lesions. The results suggest that there is a difference in the nature of DNA damage measured by filter elution at pH 9.6 vs. pH 7.2 and that a deficiency in the repair of pH 9.6-labile lesions does not contribute to cell lethality in the case of the radiation-resistant variants. The radiation resistance of these variants in comparison to strain LY-S may be due at least in part to recovery of the ability to rejoin frank DNA double-strand breaks.
Research Organization:
Case Western Reserve Univ., Cleveland, OH (USA)
OSTI ID:
7071861
Journal Information:
Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:21; ISSN PNASA
Country of Publication:
United States
Language:
English