UVB-induced mutagenesis in hairless lambda lacZ-transgenic mice.
UVB-induced mutagenesis was studied in hairless 40.6 transgenic mice (MutaMouse), which contain the lambda gt10lacZ shuttle vector as a target for mutagenesis. Mice were exposed at the dorsal side to either single doses of 200, 500, 800, or 1000 J/m2 UVB or to two successive irradiations of either 200 and 800 J/m2 UVB, with intervals of 1, 3, or 5 days, or to 800 and 200 J/m2 UVB with a 5-day interval. At 23 days after the last exposure, lacZ mutant frequencies (MF) were determined in the epidermis. The lacZ MF increased linearly with increasing dose of UVB. The mutagenic effect of two successive irradiations appeared to be additive. The UV-induced mutation spectrum was dominated by G:C --> A:T transitions at dipyrimidine sites. DNA-sequence analysis of spontaneously mutated phages showed a diverse spectrum consisting of insertions, deletions and G:C --> A:T transitions at CpG sites. The results indicate that the hairless lambda lacZ-transgenic mouse is a suitable in vivo model for studying UVB-induced mutations.
Frijhoff
A F
AF
TNO Nutrition and Food Research Institute, Department of Molecular Toxicology, Zeist, The Netherlands.
Rebel
H
H
Mientjes
E J
EJ
Kelders
M C
MC
Steenwinkel
M J
MJ
Baan
R A
RA
van Zeeland
A A
AA
Roza
L
L
D000818:Animals; D007763:Lac Operon / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D016296:Mutagenesis / Q000528:radiation effects*; D009154:Mutation; D017422:Sequence Analysis, DNA; D014466:Ultraviolet Rays