This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dahle, J. Articles by Kvam, E. Search for Related Content PubMed PubMed Citation Articles by Dahle, J. Articles by Kvam, E.

Induction of Delayed Mutations and Chromosomal Instability in Fibroblasts after UVA-, UVB-, and X-Radiation¹

Department of Biophysics, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway

Mutations in critical genes are believed to be a necessary part of cancer induction. The conventional view of radiation mutagenesis is that radiation induces most mutations in cells shortly after irradiation, because of false repair or lack of repair of DNA damage before or during DNA replication. In contrast, we here show that delayed mutations in the hypoxanthine phosphoribosyltransferase locus of Chinese hamster fibroblasts (V79) arise many cell generations after three types of carcinogenic irradiation: (a) UVA-; (b) UVB-; or (c) X-radiation. The frequency of mutations at the hypoxanthine phosphoribosyltransferase locus was measured in clones 14 days after irradiation with doses killing 80% of the cells. The proportion of unstable clones, as indicated by mutant fractions 10–7500-fold above background, was higher for the cells treated with UVA (13.2%) than for cells treated with UVB (9.2%) and X-radiation (9.6%). In contrast, UVA produces few immediate mutations compared with UVB and X-radiation. Thus, UVA-radiation, which is suspected to cause melanomas, produces few immediate mutations but more delayed mutations than UVB or X-radiation. Clones of cells that developed delayed mutations were examined for markers of chromosome instability, such as increased numbers of centrosomes, DNA content, and variability in the number of chromosomes. All radiation types increased the variability in the number of chromosomes in unstable clones. Although UVB and X-radiation, which damages DNA by direct interaction, resulted in an increased number of centrosomes in cell clones, the oxidative UVA-radiation did not. Thus, the mechanism of UVA-induced chromosomal instability is apparently different from that of UVB and X-radiation.

This article has been cited by other articles:

				Y.-Y. He, S. E. Council, L. Feng, and C. F. Chignell UVA-Induced Cell Cycle Progression Is Mediated by a Disintegrin and Metalloprotease/Epidermal Growth Factor Receptor/AKT/Cyclin D1 Pathways in Keratinocytes Cancer Res., May 15, 2008; 68(10): 3752 - 3758. [Abstract] [Full Text] [PDF]

				S. T. Durant, K. S. Paffett, M. Shrivastav, G. S. Timmins, W. F. Morgan, and J. A. Nickoloff UV Radiation Induces Delayed Hyperrecombination Associated with Hypermutation in Human Cells. Mol. Cell. Biol., August 1, 2006; 26(16): 6047 - 6055. [Abstract] [Full Text] [PDF]

				C. Berking, R. Takemoto, K. Satyamoorthy, T. Shirakawa, M. Eskandarpour, J. Hansson, P. A. VanBelle, D. E. Elder, and M. Herlyn Induction of Melanoma Phenotypes in Human Skin by Growth Factors and Ultraviolet B Cancer Res., February 1, 2004; 64(3): 807 - 811. [Abstract] [Full Text] [PDF]