Abstract
Xeroderma pigmentosum (XP) is a recessively transmitted disorder of man characterized by increased sensitivity to ultraviolet light. Homozygous, affected individuals, upon exposure to sunlight, sustain severe damage to the skin; this damage is characteristically followed by multiple basal and squamous cell carcinomas and not uncommonly by other malignant neoplasia. A tissue culture cell line was derived from the skin of a man with XP. Our measurements of ultraviolet-induced pyrimidine dimers in cellular DNA show that normal diploid human skin fibroblasts excise up to 70 per cent of the dimers in 24 hours, but that fibroblasts derived from the individual with XP excise less than 20 per cent in 48 hours. Alkaline gradient sedimentation experiments show that during the 24 hours after irradiation of normal cells a large number of single-strand breaks appear and then disappear. Such changes are not observed in XP cells. XP cells apparently fail to start the excision process because they lack the required function of an ultraviolet-specific endonuclease. These findings, plus earlier ones of Cleaver on the lack of repair replication in XP cells, raise the possibility that unexcised pyrimidine dimers can be implicated in the oncogenicity of ultraviolet radiation.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Cleaver J. E. Defective repair replication of DNA in xeroderma pigmentosum. Nature. 1968 May 18;218(5142):652–656. doi: 10.1038/218652a0. [DOI] [PubMed] [Google Scholar]
- Cleaver J. E. Xeroderma pigmentosum: a human disease in which an initial stage of DNA repair is defective. Proc Natl Acad Sci U S A. 1969 Jun;63(2):428–435. doi: 10.1073/pnas.63.2.428. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howard-Flanders P. DNA repair. Annu Rev Biochem. 1968;37:175–200. doi: 10.1146/annurev.bi.37.070168.001135. [DOI] [PubMed] [Google Scholar]
- McGrath R. A., Williams R. W. Reconstruction in vivo of irradiated Escherichia coli deoxyribonucleic acid; the rejoining of broken pieces. Nature. 1966 Oct 29;212(5061):534–535. doi: 10.1038/212534a0. [DOI] [PubMed] [Google Scholar]
- Regan J. D., Trosko J. E., Carrier W. L. Evidence for excision of ultraviolet-induced pyrimidine dimers from the DNA of human cells in vitro. Biophys J. 1968 Mar;8(3):319–325. doi: 10.1016/S0006-3495(68)86490-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- SETLOW R. B., SWENSON P. A., CARRIER W. L. THYMINE DIMERS AND INHIBITION OF DNA SYNTHESIS BY ULTRAVIOLET IRRADIATION OF CELLS. Science. 1963 Dec 13;142(3598):1464–1466. doi: 10.1126/science.142.3598.1464. [DOI] [PubMed] [Google Scholar]
- STUDIER F. W. SEDIMENTATION STUDIES OF THE SIZE AND SHAPE OF DNA. J Mol Biol. 1965 Feb;11:373–390. doi: 10.1016/s0022-2836(65)80064-x. [DOI] [PubMed] [Google Scholar]
- Setlow R. B., Carrier W. L. Pyrimidine dimers in ultraviolet-irradiated DNA's. J Mol Biol. 1966 May;17(1):237–254. doi: 10.1016/s0022-2836(66)80105-5. [DOI] [PubMed] [Google Scholar]
- Setlow R. B. Cyclobutane-type pyrimidine dimers in polynucleotides. Science. 1966 Jul 22;153(3734):379–386. doi: 10.1126/science.153.3734.379. [DOI] [PubMed] [Google Scholar]
- Setlow R. B. The photochemistry, photobiology, and repair of polynucleotides. Prog Nucleic Acid Res Mol Biol. 1968;8:257–295. doi: 10.1016/s0079-6603(08)60548-6. [DOI] [PubMed] [Google Scholar]