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Simulated solar light‐inducedp53mutagenesis in SKH‐1 mouse skin: A dose–response assessment
- Source :
- Molecular Carcinogenesis. 47:599-607
- Publication Year :
- 2008
- Publisher :
- Wiley, 2008.
-
Abstract
- Sunlight and ultraviolet-induced mutation of the p53 gene is a frequent, possibly obligate step in skin cancer development, making quantitative measurement of p53 mutation an ideal biomarker for sunlight-induced skin carcinogenesis. To understand how the appearance of p53 mutation relates to skin tumor development, SKH-1 hairless mice were exposed 5 d per week to one of four different doses of simulated solar light (SSL; 0, 6.85, 13.70, 20.55 mJ x CIE/cm(2)) previously characterized for their tumorigenic potential. Allele-specific competitive blocker-PCR (ACB-PCR) was used to measure levels of p53 codon 270 CGT to TGT mutation within DNA isolated from dorsal skin of exposed mice. For each dose, p53 mutant fraction (MF) was measured after 4, 16, and 28 wk of exposure. Significant dose- and time-dependent increases in p53 MF were identified. All p53 MF measurements were integrated by relating the observed p53 MF to the cumulative dose of SSL. The increase in the logarithm of p53 MF was described by the linear function: log(10) MF = alpha + 0.0016 x d, where alpha is the spontaneous log(10) MF after a particular time point and d is the dose of SSL in mJ x CIE/cm(2). The p53 MF induced in nontumor bearing skin by 28 wk of exposure at the high dose of SSL was significantly lower than that found in skin tumors induced by approximately 32 wk of exposure to the same dose of SSL. p53 MF showed a strong negative correlation with tumor latency, suggesting this quantitative biomarker has the potential to predict tumorigenicity.
- Subjects :
- Cancer Research
Neoplasms, Radiation-Induced
Skin Neoplasms
Ultraviolet Rays
Mutant
Alpha (ethology)
Biology
medicine.disease_cause
Polymerase Chain Reaction
Mice
Biomarkers, Tumor
medicine
Animals
Molecular Biology
Alleles
Skin
Dose-Response Relationship, Drug
integumentary system
Cumulative dose
Mutagenesis
Genes, p53
medicine.disease
Molecular biology
Hairless
Dose–response relationship
Mutation
Immunology
Sunlight
Electrophoresis, Polyacrylamide Gel
Skin cancer
Carcinogenesis
Subjects
Details
- ISSN :
- 10982744 and 08991987
- Volume :
- 47
- Database :
- OpenAIRE
- Journal :
- Molecular Carcinogenesis
- Accession number :
- edsair.doi.dedup.....db036f7c2154bc43817e0e28147486f7
- Full Text :
- https://doi.org/10.1002/mc.20415