Hyperthermia induces resistance to ultraviolet light B in primary and immortalized epidermal keratinocytes.
Environmental exposure to UVB (290-320 nm) wavelengths of the solar spectrum causes major damage, including carcinogenesis, in the skin. Therefore, cellular responses that protect against UVB damage are of particular interest in cutaneous epithelial cells. In cultured keratinocytes, mild hyperthermia generates a classical stress response with acquired thermotolerance and elevated stress protein synthesis (E. V. Maytin, J. Biol. Chem., 267: 23189-23196, 1992). To test the ability of this stress response to protect against UVB damage, monolayers of primary murine keratinocytes or BALB/MK keratinocytes were heated at 42 degrees C for 1 h and then exposed to UVB at 6 h (typical dose, 40 mJ/cm2). Survival was assessed by fluorescein diacetate/ethidium bromide vital dye uptake and video microscopy. With heat-conditioning prior to UVB, a significant increase in both the percentage viability (2- to 3-fold) and in the absolute number of living (fluorescein diacetate-positive) cells was measurable at 24-48 h. Steady-state incorporation into [3H]DNA and 35S-protein, while suppressed immediately after UVB, showed greater recovery in heat-conditioned cultures compared to sham-conditioned cultures at 48 h. Increased metabolic activity was accompanied by increased proliferative potential since colonies of BALB/MK cells observed at 72 h were larger, more numerous, and more active in the uptake of 5-bromo-2'-deoxyuridine in heat-conditioned cultures. A time course for the development of UVB resistance showed maximal protection when heat and UVB were spaced approximately 6 h apart. Hyperthermic conditioning could induce UVB protection in nonproliferating cells, indicating that cell cycle arrest was not primarily responsible for the UVB-protective effect. In summary, hyperthermia induces a mechanism in epithelial cells which can ameliorate damage from UVB.
Maytin
E V
EV
Cutaneous Biology Research Center, Department of Dermatology, Massachusetts General Hospital, Boston.
Murphy
L A
LA
Merrill
M A
MA
D000818:Animals; D000831:Animals, Newborn; D002470:Cell Survival / Q000528:radiation effects*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D004247:DNA / Q000096:biosynthesis; D004307:Dose-Response Relationship, Radiation; D004817:Epidermis; D006358:Hot Temperature; D015603:Keratinocytes / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects*; D007700:Kinetics; D008715:Methionine / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D014176:Protein Biosynthesis; D013936:Thymidine / Q000378:metabolism; D014466:Ultraviolet Rays
D004247:DNA; D008715:Methionine; D013936:Thymidine