title: The dose dependence of cyclobutane dimer induction and repair in UVB-irradiated human keratinocytes.
abstract: UVB and UVA components of the solar spectrum or from artificial UV-sources might be important etiological factors for the induction and development of skin cancer. In particular, deficiencies in the capacity to repair UV-induced DNA-lesions have been linked to this phenomenon. However, until now only limited data are available on the biological and physical parameters governing repair capacity. We have, therefore, developed a flowcytometric assay using fluorescence-labeled monoclonal antibodies to study the dose-dependence of induction and repair of UVB-induced cyclobutane pyrimidine dimers in a spontaneously immortalized keratinocytic cell line (HaCaT). Our results show that the kinetics of recognition and incision of UVB-induced DNA lesions slows down by a factor of about 3 in a dose range of 100-800 J m-2. Furthermore, a thorough analysis of repair kinetics indicates that this reduction in repair capacity might not be dependent on saturation of enzymatic repair capacity (Michaelis-Menten) but may be caused by a UV-induced impairment of enzymes involved in DNA repair. Because this effect is evident in vitro at doses comparable to the minimal erythemal dose in vivo, our results might have significant impact on risk assessment for UV-induced carcinogenesis.
authors: Dermatologisches Zentrum Buxtehude, Krankenhaus Buxtehude, Germany. dermatologie@hospit.std.shuttle.de
authors: R
authors: R
authors: Greinert
authors: O
authors: O
authors: Boguhn
authors: D
authors: D
authors: Harder
authors: E W
authors: EW
authors: Breitbart
authors: D L
authors: DL
authors: Mitchell
authors: B
authors: B
authors: Volkmer
mesh_terms: D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D009381:Neoplasms, Radiation-Induced / Q000209:etiology; D018462:Photobiology; D011740:Pyrimidine Dimers / Q000378:metabolism* / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology; D014466:Ultraviolet Rays / Q000009:adverse effects
chemical_list: D011740:Pyrimidine Dimers