Photocarcinogenesis and susceptibility to UV radiation in the v-Ha-ras transgenic Tg.AC mouse.
The v-Ha-ras transgenic Tg.AC mouse line has proven to be a useful model for the study of chemical carcinogenic potential. We undertook experiments designed to study the effect of the physical carcinogen, UV radiation, on tumorigenesis in this mouse strain. Following a total of three exposures on alternating days to a radiation source covering a cumulative UVR exposure range of 2.6-42.6 kJ per m2, squamous papillomas developed by 4 wk after initial exposure in a dose-dependent manner. Malignancies developed within 18-30 wk following the initial UVR exposure and were all diagnosed as squamous cell carcinoma or spindle cell tumors. In contrast to other mouse stains used in photocarcinogenesis studies, few p53 mutations were found in Tg.AC malignancies upon polymerase chain reaction-single stranded conformational polymorphism analysis of exons 4-8 followed by sequencing of suspicious bands; however, all tumors analyzed by in situ hybridization expressed the v-Ha-ras transgene. Immunohistochemical analysis of UVR-exposed skin taken 24 h after the last of three exposures (13.1 kJ per m2 total UVR) showed expression of p53 in hair follicles and in interfollicular epidermis, which indicates that the gene was functional. Thus, although there are some differences between the Tg.AC and other mouse models, these results suggest that the Tg.AC mouse may be a useful model for the study of acute exposure photocarcinogenesis.
Trempus
C S
CS
Laboratory of Environmental Carcinogenesis and Mutagenesis, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
Mahler
J F
JF
Ananthaswamy
H N
HN
Loughlin
S M
SM
French
J E
JE
Tennant
R W
RW
D000818:Animals; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D005260:Female; D016158:Genes, p53; D011905:Genes, ras; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology*; D010212:Papilloma / Q000209:etiology*; D010641:Phenotype; D011836:Radiation Tolerance; D014466:Ultraviolet Rays