The role of DNA modifications in carcinogenesis and immunosuppression after exposure of human skin to UV-B radiation

Objective

Ultraviolet radiation in sunlight is thought to be responsible for the induction of skin tumors. More recently it appeared that exposure of the skin to ultraviolet B (UVB) radiation also results in systemic suppression of the immune system. The latter effect can contribute to an increase in the number of patients suffering from infectious diseases and skin cancer.
Photon absorption produces reactive intermediates, e.g. triplet excited states, singlet oxygen and free radicals, and is the primary step of the interaction of UVB radiation with skin cells, followed by damage to essential biomolecules, such as DNA. Damage to cellular DNA of the skin has been implicated in photocarcinogenesis and UVB-induced immunosuppression. Our aim is to relate UVB-induced DNA damage and its repair to biological effects resulting from UVB irradiation, such as enhanced expression of relevant mRNA molecules, mutagenesis, modulation of cytokine levels as well as immunosuppression in vivo.
Besides animal models, human keratinocytes will be used. The latter will be derived from sun-protected and frequently sun-exposed skin areas of young and aged individuals, as well as from actinic keratoses and squamous cell carcinomas.
The types of DNA damage and their relative amounts will be measured with biochemical, physico-chemical, and immunochemical techniques. The effect of anti-oxidants on the occurrence of certain types of UVB-induced DNA damage and on the related biological effects will also be assessed. From this information the contribution of certain types of UVB-induced cellular damage to skin cancer and immunosuppression may be resolved. This knowledge will provide a scientific basis for protective or prophylactic measures that may be effective in cancer prevention.

Fields of science

• natural sciences › biological sciences › genetics › DNA
• natural sciences › biological sciences › biochemistry › biomolecules
• medical and health sciences › health sciences › infectious diseases
• medical and health sciences › clinical medicine › oncology › skin cancer › squamous cell carcinoma
• medical and health sciences › basic medicine › immunology

Programme(s)

• FP3-ENV 1C - Specific research and technological development programme (EEC) in the field of the environment, 1990-1994

Topic(s)

• 040203 - Environment and human health

Call for proposal

Data not available

Funding Scheme

CSC - Cost-sharing contracts

Coordinator

NETHERLANDS ORGANISATION FOR APPLIED SCIENTIFIC RESEARCH - TNO

Address

48,utrechtseweg 48
3700 AJ Zeist
Netherlands

Participants (3)

Bayerische Julius-Maximilians-Universität Würzburg

Germany

Address

Versbacher Straße
97078 Würzburg

Katholieke Universiteit Leuven

Belgium

Address

49,herestraat
3000 Leuven

LEIDEN UNIVERSITY

Netherlands

Address

55,einsteinweg 55 Gorlaeus Laboratories
2333 CC Leiden