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Photocarcinogenesis: UVA vs. UVB radiation
1Department of Dermatology, Leiden University Medical Center/LUMC, Leiden, Netherlands. F.R.de_Gruijl@lumc.nl
Abstract:
Recent research is revealing combinations of disturbed oncogenic and tumor-suppressive signaling pathways by altered or missing genes in skin cancers: mutated PTCH (in the mitogenic Sonic Hedgehog pathway) and mutated p53 tumor suppressor gene in basal cell carcinomas (BCC), possibly an activated mitogenic RAS pathway and mutated p53 in squamous cell carcinomas (SCC), and possibly an activated MET/RAS pathway and inactive p16(INK4a) tumor suppressor in cutaneous melanomas. UV radiation damages DNA and can give rise to genomic alterations, varying from point mutations to crude chromosomal dislocations. UVB radiation (wavelength band 280-315 nm) is more carcinogenic than UVA radiation (315-400 nm) in experimental induction of SCC. The impact of UVB radiation can be clearly inferred from the characteristic point mutations in p53 found in human SCC and BCC. In contrast to UVB radiation, much of the mutagenic and carcinogenic action of UVA radiation appears to be mediated through reactive oxygen species (ROS). Experiments have shown that UVA1 (340-400 nm) exposure induces SCC largely without the characteristic point mutations in p53. Both UVB and UVA radiation can give rise to ROS-related point mutations (e.g. G to T) and crude genomic alterations (e.g. deletions) which may not be recognized as caused by UV radiation.
Insights
Skin cancers involve genetic mutations in key pathways. UV radiation, particularly UVB, causes DNA damage and mutations, while UVA generates reactive oxygen species, leading to various genomic alterations.
Area of Science:
- Oncology
- Dermatology
- Molecular Biology
Background:
- Skin cancers like basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma arise from disrupted oncogenic and tumor-suppressive signaling pathways.
- Specific genetic alterations include mutated PTCH and p53 in BCC, activated RAS and mutated p53 in SCC, and activated MET/RAS with inactive p16(INK4a) in melanoma.
- Ultraviolet (UV) radiation is a known carcinogen, inducing DNA damage and genomic instability.
Purpose of the Study:
- To elucidate the specific genetic pathways and DNA damage mechanisms involved in different types of skin cancer.
- To differentiate the carcinogenic roles and mutagenic effects of UVB and UVA radiation in skin carcinogenesis.
- To understand how UV radiation-induced genomic alterations contribute to the development of skin cancers.
Main Methods:
- Analysis of genetic mutations in oncogenic and tumor-suppressive pathways in various skin cancers.
- Experimental studies comparing the carcinogenicity and mutagenic potential of UVB and UVA radiation.
- Investigation of DNA damage types, including point mutations and chromosomal aberrations, induced by different UV wavelengths.
Main Results:
- UVB radiation is more carcinogenic in inducing SCC than UVA radiation.
- UVB exposure leads to characteristic p53 point mutations in human SCC and BCC.
- UVA radiation's carcinogenic effects are largely mediated by reactive oxygen species (ROS), inducing mutations and genomic alterations, sometimes without the typical p53 mutations seen with UVB.
Conclusions:
- Distinct genetic pathway disturbances characterize different skin cancers.
- UVB and UVA radiation possess different mechanisms of DNA damage and carcinogenicity.
- Both UVB and UVA contribute to skin cancer development through various point mutations and genomic alterations, with UVA's role often linked to ROS-mediated damage.