Cytotoxic, mutagenic and carcinogenic properties of ultraviolet radiation : shining light on photolesions

摘要: textabstractExposure to ultraviolet light (UV light) poses a serieus threat human health. An altered life style (holidays in the sun, tanning devices) has led increased exposure UV Western population. damages DNA, carrier of genetic information, which can result in permanent alterations genome and, ultimately, cancer. The majority DNA lesions induced by consists cyclobutane pyrimidine dimers (CPDs) and pyrimidine-(6,4)-pyrimidone photoproducts (6-4PPs). relative contribution these CPDs 6-4PPs effects acute and chronic exposure, however, is nat known (e.g. sunburn, cancer). Although organisms are equipped with nucleotide excision repair (NER) mechanism for remaval lesions, this mechanism may offer sufficient proteetion cases excessive light. aim thesis is to further elucidate mechanisms behind detrimental determine the role individual classes UV-induced processes. To end, we generated mice transgenically expressing photolyase enzymes. This approach enables light-controlled of a single type lesion, allowing investigation responses. In Chapter 1, review current knowledge on damage repair, the consequences Chapters 2 3 describe generation of ubiquitously CPD 6-4PP transgenie mice. We show that marsupial and plant gene products are functional mice, resulting light-dependent DNA lesions from mouse skin. Furthermore, provide evidence responsible adverse UV effects including cell death, sunburn permanent genomic (mutations). In 4 we mice keratinocyte-specific K14 promoter, fast by photoreactivation basal keratinocytes the epidermis, whereas other types such as fibroblasts Langerhans cells repaired in slow fashion (if at all). gave us unique opportunity dissect involved in UV responses. 5 carcinogenic potential studied. Importantly, we show alone delay induction skin cancer great extent. An important carcinogenesis performed immune system. show that not only protects animal lowering mutation laad, but it also abclishes immunosuppression, system respond adequately to malignancies. results described reviewed general discussion 6.