Induction of delayed mutations and chromosomal instability in fibroblasts after UVA-, UVB-, and X-radiation.
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.
Dahle
Jostein
J
Department of Biophysics, The Norwegian Radium Hospital, Montebello, 0310 Oslo, Norway. Jostein.Dahle@labmed.uio.no
Kvam
Egil
E
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D033481:Chromosomes, Mammalian / Q000528:radiation effects*; D006224:Cricetinae; D003412:Cricetulus; D004249:DNA Damage; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000528:radiation effects*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D009154:Mutation; D014466:Ultraviolet Rays / Q000009:adverse effects*; D014965:X-Rays / Q000009:adverse effects*
D007041:Hypoxanthine Phosphoribosyltransferase