Development and characterization of a novel skin model for cutaneous phototoxicology.
The biological consequences of exposure to ultraviolet radiation (UV) has been receiving increased attention. Most known biological effects (such as sunburn and skin cancer) are attributed to mid-wave UVB (290-320 nm) exposure. Phototoxicity, a nonimmunological UV-induced response, has been studied using in vivo (human and animal) and in vitro models. Ethical considerations and model limitations underscore the need for a reliable in vitro model to assess cutaneous phototoxicity that would ideally possess viable cells and have a normal anatomical structure with an intact and functional vasculature. This would allow therapeutic or preventive drugs to be tested in a system in which their disposition (cutaneous concentration-time profile) has been shown to be similar to the in vivo setting. In addition, morphological, biochemical and physiological changes should be easily monitored within the same system. The purpose of this study was to characterize the isolated perfused porcine skin flap (IPPSF) developed in our laboratory as a model for UVB exposure. IPPSFs (n > or = 4/treatment) were irradiated with UVB doses of 1260 mJ/cm2, 630 mJ/cm2, 315 mJ/cm2 or 0 mJ/cm2 both in vitro and in situ. Biomarkers used to assess phototoxicity demonstrated a decrease in glucose utilization, an increase in vascular resistance (pressure/flow) and an increase in the release of PGE2. Morphologically, intracellular and intercellular epidermal edema and sunburn (pyknotic) cells (SBC) increased with dose.(ABSTRACT TRUNCATED AT 250 WORDS)
Monteiro-Riviere
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NA
Cutaneous Pharmacology and Toxicology Center, North Carolina State University, Raleigh 27606, USA.
Inman
A O
AO
Riviere
J E
JE
D000818:Animals; D015415:Biomarkers / Q000032:analysis; D017484:Dermatitis, Phototoxic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D004487:Edema / Q000473:pathology; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D010477:Perfusion; D012867:Skin / Q000378:metabolism / Q000473:pathology; D012871:Skin Diseases / Q000473:pathology; D013471:Sunburn / Q000473:pathology; D013524:Surgical Flaps; D013552:Swine; D014466:Ultraviolet Rays / Q000009:adverse effects; D014655:Vascular Resistance / Q000502:physiology
D015415:Biomarkers; D005947:Glucose; D015232:Dinoprostone