title: Single UVB overexposure stimulates melanocyte proliferation in murine skin, in contrast to fractionated or UVA-1 exposure.
abstract: Overexposure to short- and long-wave ultraviolet radiations (UVB, UVA) may contribute to melanoma development through combined genotoxic and mitogenic effects in melanocytes. This study compares the impact of UVA-1 versus UVB, and single versus fractionated exposures on melanocyte proliferation in hairless SKH-2 mice. A single erythemal dose was compared with an equal dose fractionated over 8 d, and dose-dependency was studied. Proliferation (Ki-67 positive-sign) in melanocytes (melanoma antigen recognized by T-cells-1 positive or micropthalmia transcription factor positive) was ascertained in double-labeled skin sections. Single erythemal UVB exposures caused a delayed, dose-dependent increase of melanocyte proliferation. The highest, 17-fold, increase (from 0.05% to 0.8% of melanocytes) occurred 4 d after UVB exposure, without any detectable effect on overall melanocyte numbers. Correspondingly, DNA repair-deficient xeroderma pigmentosum A (Xpa) mice proved exquisitely sensitive to melanocyte proliferation induction by UVB exposure. No discernable effects were measured from fractionated suberythemal UVB exposures, or from any UVA-1 exposure regimen. Hence, melanocyte proliferation appears to be most efficiently induced by a single UVB overexposure. Moreover, the ineffectiveness of UVA-1 radiation and the enhanced sensitivity of Xpa mice point at pyrimidine dimers as causative DNA lesions. Consequently, murine nevi and melanoma are expected to be most effectively induced by intermittent UVB overexposures.
authors.affiliation: Dermatology Department, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Arne
authors.initials: A
authors.lastname: van Schanke
authors.forename: Marjan J
authors.initials: MJ
authors.lastname: Jongsma
authors.forename: Roel
authors.initials: R
authors.lastname: Bisschop
authors.forename: Gemma M C A L
authors.initials: GM
authors.lastname: van Venrooij
authors.forename: Heggert
authors.initials: H
authors.lastname: Rebel
authors.forename: Frank R
authors.initials: FR
authors.lastname: de Gruijl
mesh_terms: D000818:Animals; D002455:Cell Division / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics; D004817:Epidermis / Q000473:pathology* / Q000528:radiation effects*; D004890:Erythema; D006965:Hyperplasia; D008544:Melanocytes / Q000473:pathology* / Q000528:radiation effects*; D051379:Mice; D008812:Mice, Hairless; D018345:Mice, Knockout; D011740:Pyrimidine Dimers / Q000528:radiation effects; D011829:Radiation Dosage; D013936:Thymidine; D014466:Ultraviolet Rays / Q000009:adverse effects*; D051760:Xeroderma Pigmentosum Group A Protein
chemical_list: D004268:DNA-Binding Proteins; D011740:Pyrimidine Dimers; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; D013936:Thymidine