Characterization of mutations induced by 300 and 320 nm UV radiation in a rat fibroblast cell line.
The cytotoxic and mutagenic activities of monochromatic ultraviolet light (UV) at four wavelengths (254, 290, 300 and 320 nm) were determined using a rat fibroblast cell line CREF stably infected with a retroviral vector carrying the neo and HSV-tk markers. In this system, mutations can be positively detected as acyclovir-resistant colonies. Although the action spectra for these activities closely fit some of the previously reported spectra for photochemical DNA modifications, erythema, cell killing and mouse skin carcinogenesis, they diverge at 320 nm from the absorption spectrum for DNA and the action spectrum for bacterial inactivation and mutagenesis. Structural comparison of the HSV-tk mutants detected after irradiation with 300 and 320 nm UV revealed (1) CC dimers and C oligomers as predominant targets at both wavelengths; (2) increased incidence of relatively large deletions at 300 nm; and (3) greatly increased frequency of tandem double mutations at both wavelengths and of clustered multiple mutations at 320 nm. These results suggest the involvement of distinct mechanisms specifically operating, or becoming evident, in UV-mediated mutagenesis at these different wavelengths in mammalian cells.
Akiyama
N
N
Department of Molecular Oncology, Kyoto University Graduate School of Medicine, Japan.
Alexander
D
D
Aoki
Y
Y
Noda
M
M
D000212:Acyclovir / Q000494:pharmacology; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D000998:Antiviral Agents / Q000494:pharmacology; D001483:Base Sequence; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects*; D005822:Genetic Vectors / Q000235:genetics; D019868:Kanamycin Kinase; D008969:Molecular Sequence Data; D009152:Mutagenicity Tests / Q000379:methods; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D016133:Polymerase Chain Reaction; D051381:Rats; D012190:Retroviridae / Q000235:genetics; D017422:Sequence Analysis, DNA; D018139:Simplexvirus / Q000201:enzymology / Q000235:genetics; D013937:Thymidine Kinase / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D014158:Transcription, Genetic; D014466:Ultraviolet Rays
D000963:Antimetabolites; D000998:Antiviral Agents; D017853:Phosphotransferases (Alcohol Group Acceptor); D013937:Thymidine Kinase; D019868:Kanamycin Kinase; D000212:Acyclovir