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UV-induced DNA damage in humans

thesis
posted on 2024-09-03, 02:30 authored by Vladimir J Bykov
<p>Ultraviolet radiation is considered to be the most harmful part of solar energy affecting man. The depletion of the ozone layer around the Earth increases the total exposure to UV-light. The incidence of skin cancer in man has been shown to be associated with exposure to solar radiation, especially to UV-light. UV is capable of initiating skin carcinogenesis through DNA damage, particularly by formation of DNA photoproducts. The major products formed by UV irradiation are dipyrimidine compounds, namely cyclobutane dimers and 6-4 photoproducts. A high mutation frequency at pyrimidine sites in skin tumours provides additional evidence for the relationship between UV-induced DNA damage and skin cancer.</p><p>The research program was focused on the development and application of a highly specific and sensitive 32P-HPLC method for the study of UV-induced DNA damage in humans.</p><p>* The application of the developed method to human studies demonstrated that one minimal erythema dose of solar- simulated radiation is capable of inducing levels of DNA damage far exceeding any other known external exposure. This finding may explain the high frequency of skin cancer among other tumours</p><p>* There is a large interindividual variation in the induction of photoproducts after exposure to a uniform physical dose of solar-simulated radiation.</p><p>* There is no association between erythemal response and induction of DNA damage.</p><p>* The reparability of dipyrimidine lesions dependent on the dipyrimidine pair forming a lesion, implicating sequence-specificity of the repair process.</p><p>* There is a large interindividual variation in the rates of DNA repair process.</p><p>Taken all our results together, we have shown that human response to solar- simulated radiation is highly individual. The level of immediate damage may vary for a given acute biological dose and repair rates may vary. At present, we have no evidence that these two aspects are coupled in any way. Thus, a combination of proneness to damage along with poor repair may predispose individuals to skin cancer.</p>

History

Defence date

1999-01-15

Department

  • Department of Medicine, Huddinge

Publisher/Institution

Karolinska Institutet

Publication year

1999

Thesis type

  • Doctoral thesis

ISBN-10

91-628-3345-6

Language

  • eng

Original publication date

1998-12-25

Author name in thesis

Bykov, Vladimir J

Original department name

Biosciences and Nutrition

Place of publication

Stockholm

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