UVB-induced gpt mutations in the skin of gpt delta transgenic mice

Ultraviolet light B (UVB)-induced mutagenesis was studied in gpt delta tran sgenic mice, which contain the lambda EG10 shuttle vector as a transgene. T he 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 g pi gene were determined in the epidermis and the dermis, and the gpi mutati ons in the epidermis were identified by DNA sequencing. The epidermis exhib ited 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 th ose of the nonirradiated mice, whereas the MF of the dermis were only two t o three times higher than the nonirradiated level at the doses used. The UV B-induced mutation spectrum in the epidermis was dominated by G:C to A:T tr ansitions at dipyrimidine sires, 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 observe d at different sites in UVB-irradiated and nonirradiated mice. These result s indicate that gpt delta transgenic mouse is a suitable model For studying in vivo UVB-induced mutations at the molecular level. (C) 1999 Wiley-liss, Inc.