p53 Mutations in hairless SKH-hr1 mouse skin tumors induced by a solar simulator.
In this study, we investigated whether the spectrum of p53 mutations in skin tumors induced in hairless SKH-hr1 mice by a solar simulator (290-400 nm) are similar to those found in skin tumors induced in C3H mice by UV radiation from unfiltered (250-400 nm) and Kodacel-filtered (290-400 nm) FS40 sunlamps. Analysis of tumor DNA for p53 mutations revealed that 14 of 16 (87.5%) SkH-hr1 skin tumors induced by the solar simulator contained mutations. Single C-->T transitions at dipyrimidine sequences located on the nontranscribed DNA strand were the most predominant type of p53 mutation. Remarkably, 52% of all p53 mutations in solar simulator-induced SKH-hr1 skin tumors occurred at codon 270, which is also a hotspot in C3H skin tumors induced by unfiltered and Kodacel-filtered FS40 sunlamps. However, T-->G transversions, which are hallmarks of UVA-induced mutations, were not detected in any of the solar simulator-induced skin tumors analyzed. These results demonstrate that the p53 mutation spectra seen in solar simulator-induced SKH-hr1 skin tumors are similar to those present in -unfiltered and Kodacel-filtered FS40 sunlamp-induced C3H skin tumors. In addition, our data indicate that the UVA present in solar simulator radiation does not play a role in the induction of p53 mutations that contribute to skin cancer development.
Ananthaswamy
H N
HN
Department of Immunology, University of Texas M. D. Anderson Cancer Center, Houston 77030, USA. hanantha@notes.mdacc.tmc.edu
Fourtanier
A
A
Evans
R L
RL
Tison
S
S
Medaisko
C
C
Ullrich
S E
SE
Kripke
M L
ML
D000818:Animals; D016466:CHO Cells; D002294:Carcinoma, Squamous Cell / Q000209:etiology* / Q000235:genetics*; D006224:Cricetinae; D005260:Female; D016158:Genes, p53; D051379:Mice; D008812:Mice, Hairless; D008809:Mice, Inbred C3H; D009154:Mutation; D012878:Skin Neoplasms / Q000209:etiology* / Q000235:genetics*; D013472:Sunlight / Q000009:adverse effects*