UVB-induced gpt mutations in the skin of gpt delta transgenic mice.
Ultraviolet light B (UVB)-induced mutagenesis was studied in gpt delta transgenic mice, which contain the lambdaEG10 shuttle vector as a transgene. The mice were exposed to UVB at single doses of 0.3, 0.5, 1.0, 1.5, and 2.0 kJ/m(2). At 4 weeks after irradiation, the mutant frequencies (MF) of the gpt gene were determined in the epidermis and the dermis, and the gpt mutations in the epidermis were identified by DNA sequencing. The epidermis exhibited a higher sensitivity to UVB than the dermis at doses of 0.3 and 0.5 kJ/m(2) UVB: the MF of the epidermis were more than nine times higher than those of the nonirradiated mice, whereas the MF of the dermis were only two to three times higher than the nonirradiated level at the doses used. The UVB-induced mutation spectrum in the epidermis was dominated by G:C to A:T transitions at dipyrimidine sites, such as 5'-TC-3', 5'-CC-3', and 5'-T/C-CG-3'. Tandem transitions such as CC to TT were also observed. Interestingly, a remarkable bias towards the template strand of the gpt gene was observed in the single transitions at 5'-TC-3' and 5'-CC-3' sites, but not at 5'-T/C-CG-3' site. In contrast, G:C to A:T transitions at CpG sites and deletions were observed in nonirradiated mice. Hot spots of transitions were observed at different sites in UVB-irradiated and nonirradiated mice. These results indicate that gpt delta transgenic mouse is a suitable model for studying in vivo UVB-induced mutations at the molecular level.
Horiguchi
M
M
Division of Genetics and Mutagenesis, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan.
Masumura
K
K
Ikehata
H
H
Ono
T
T
Kanke
Y
Y
Sofuni
T
T
Nohmi
T
T
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D001483:Base Sequence; D004247:DNA; D004307:Dose-Response Relationship, Radiation; D029968:Escherichia coli Proteins; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010430:Pentosyltransferases; D011506:Proteins; D012867:Skin / Q000528:radiation effects*; D014466:Ultraviolet Rays
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D011506:Proteins; D004247:DNA; D010430:Pentosyltransferases; C071962:Gpt protein, E coli