Abstract
Cultures of fibroblasts from newborn rats and successive subcultures of these cells were treated with 4-nitroquinoline-1-oxide to induce DNA repair. DNA from the cultures was examined by velocity sedimentation in alkaline sucrose gradients immediately after drug treatment and after a post-treatment incubation period of 3 h. Early passage cells were able to repair the damage that appeared as single strand breaks, however, by the seventh subculture this activity was not apparent. Measurements of repair synthesis showed a partial loss of this capacity with successive subculture. The results fit a model in which 4NQO causes two kinds of DNA modification, one of which is alkali labile and appears as a single- strand break. Both modifications are subject to excision repair, but each is recognized initially by a specific endonuclease. In the late passage cells, the endonuclease specific for the alkali labile modification is absent.
Full Text
The Full Text of this article is available as a PDF (325.2 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aaronson S. A., Hartley J. W., Todaro G. J. Mouse leukemia virus: "spontaneous" release by mouse embryo cells after long-term in vitro cultivation. Proc Natl Acad Sci U S A. 1969 Sep;64(1):87–94. doi: 10.1073/pnas.64.1.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chan A. C., Walker I. G. Reduced DNA repair during differentiation of a myogenic cell line. J Cell Biol. 1976 Sep;70(3):685–691. doi: 10.1083/jcb.70.3.685. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hart R. W., Setlow R. B. Correlation between deoxyribonucleic acid excision-repair and life-span in a number of mammalian species. Proc Natl Acad Sci U S A. 1974 Jun;71(6):2169–2173. doi: 10.1073/pnas.71.6.2169. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ikenaga M., Ichikawa-Ryo H., Kondo S. The major cause of inactivation and mutation by 4-nitroquinoline 1-oixde in Escherichia coli: excisable 4NQO-purine adducts. J Mol Biol. 1975 Feb 25;92(2):341–356. doi: 10.1016/0022-2836(75)90233-8. [DOI] [PubMed] [Google Scholar]
- Klímek M. Thymine dimerization in L-strain mammalian cells after irradiation with ultraviolet light and the search for repair mechanisms. Photochem Photobiol. 1966 Aug;5(8):603–607. doi: 10.1111/j.1751-1097.1966.tb05806.x. [DOI] [PubMed] [Google Scholar]
- Lieberman M. W., Poirier M. C. Deoxyribonucleoside incorporation during DNA repair of carcinogen-induced damage in human diploid fibroblasts. Cancer Res. 1973 Sep;33(9):2097–2103. [PubMed] [Google Scholar]
- Lieberman M. W., Poirier M. C. Intragenomal distribution of DNA repair synthesis: repair in satellite and mainband DNA in cultured mouse cells. Proc Natl Acad Sci U S A. 1974 Jun;71(6):2461–2465. doi: 10.1073/pnas.71.6.2461. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Painter R. B., Cleaver J. E. Repair replication, unscheduled DNA synthesis, and the repair of mammalian DNA. Radiat Res. 1969 Mar;37(3):451–466. [PubMed] [Google Scholar]
- Stich H. F., San R. H., Kawazoe Y. Increased sensitivity of xeroderma pigmentosum cells to some chemical carcinogens and mutagens. Mutat Res. 1973 Jan;17(1):127–137. doi: 10.1016/0027-5107(73)90261-3. [DOI] [PubMed] [Google Scholar]
- Walker I. G., Ewart D. F. Repair synthesis of DNA in HeLa and L-cells following treatment with methylnitrosourea or ultraviolet light. Can J Biochem. 1973 Feb;51(2):148–157. doi: 10.1139/o73-020. [DOI] [PubMed] [Google Scholar]
- Walker I. G., Sridhar R. The formation and repair of single-strand breaks in DNA of cultured mammalian cells treated with UV-light, methylating agents or 4-nitroquinoline-1-oxide. Chem Biol Interact. 1976 Mar;12(3-4):229–239. doi: 10.1016/0009-2797(76)90039-9. [DOI] [PubMed] [Google Scholar]