This study is aimed to determine the characteristics of the trends in incidence of basal cell carcinoma (BCC) in the Netherlands. We used incidence data of BCC from the Eindhoven Cancer Registry (Comprehensive Cancer Centre South) in the south of the Netherlands from 1973 to 2000. Data were age-adjusted and age-specific rates were calculated. Joinpoint and age-period-birth cohort modelling were applied. Between 1973 and 2000, age-adjusted incidence rates of BCC increased in both sexes, most markedly among (young) females. Recent increases were most marked on the trunk. The male data fitted age-drift models, suggesting a linear increase in rates over time, not attributable to either period- or cohort effects. In females, age-cohort-drift models described the data adequately, suggesting changes in intermittent UV exposures in subsequent cohorts. Incidence of BCC in the Netherlands is increasing rapidly, especially at body sites that are not chronically exposed to sunlight. The most likely explanation is an increased intermittent overexposure to UV radiation. This could have introduced an equal fractional increase in risk at all ages in all cohorts. There is no indication of an end to this trend in BCC.

The role of UVA-radiation-the major fraction in sunlight-in human skin carcinogenesis is still elusive. We here report that different UVA exposure regime (4 Â 5 J/cm 2 per week or 1 Â 20 J/cm 2 per week) caused tumorigenic conversion (tumors in nude mice) of the HaCaT skin keratinocytes. While tumorigenicity was not associated with general telomere shortening, we found new chromosomal changes characteristic for each recultivated tumor. Since this suggested a nontelomere-dependent relationship between UVA irradiation and chromosomal aberrations, we investigated for alternate mechanisms of UVA-dependent genomic instability. Using the alkaline and neutral comet assay as well as c-H2AX foci formation on irradiated HaCaT cells (20-60 J/cm 2 ), we show a dosedependent and long lasting induction of DNA single and double (ds) strand breaks. Extending this to normal human skin keratinocytes, we demonstrate a comparable damage response and, additionally, a significant induction and maintenance of micronuclei (MN) with more acentric fragments (indicative of ds breaks) than entire chromosomes particularly 5 days post irradiation. Thus, physiologically relevant UVA doses cause long-lasting DNA strand breaks, a prerequisite for chromosomal aberration that most likely contribute to tumorigenic conversion of the HaCaT cells. Since normal keratinocytes responded similarly, UVA may likewise contribute to the complex karyotype characteristic for human skin carcinomas.

Exposure to UV-B radiation impairs immune responses in mammals by inhibiting especially Th1-mediated contact hypersensitivity and delayed-type hypersensitivity. Immunomodulation is not restricted to the exposed skin, but is also observed at distant sites, indicating the existence of mediating factors such as products from exposed skin cells or photoactivated factors present in the superficial layers. DNA damage appears to play a key role, because enhanced nucleotide excision repair (NER) strongly counteracts immunosuppression. To determine the effects of the type and genomic location of UV-induced DNA damage on immunosuppression and acute skin reactions (edema and erythema) four congenic mouse strains carrying different defects in NER were compared: CSB and XPC mice lacking transcription-coupled or global genome NER, respectively, as well as XPA and TTD/XPD mice carrying complete or partial defects in both NER subpathways, respectively. The major conclusions are that 1) transcription-coupled DNA repair is the dominant determinant in protection against acute skin effects; 2) systemic immunomodulation is only affected when both NER subpathways are compromised; and 3) sunburn is not related to UV-B-induced immunosuppression.

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an 8 week course of weekly, frontal half-body irradiation with UVB, at 0.5 MED, leads to an significant increase in 25(OH)D serum levels, but this period is too short to reach vitamin D sufficiency.