A Novel In Vivo Model for Evaluating Agents that Protect Against Ultraviolet A-induced Photoaging

Abstract

Increasing evidence demonstrates that ultraviolet A radiation (UVA) contributes to photoaging, which results in the accumulation of massive amounts of abnormal elastic material in the dermis of photoaged skin. To study UVA-induced photoaging in an in vivo system, we utilized a line of transgenic mice containing the human elastin promoter linked to a chloramphenicol acetyl transferase reporter gene. Our prior work demonstrates promoter activation in response to ultraviolet B radiation (UVB), UVA, and psoralen plus ultraviolet A radiation in the skin of these mice. The addition of psoralen (8-MOP) prior to administration of UVA results in substantial increases in promoter activation, as compared with UVA alone. To demonstrate the utility of these mice as a model of UVA-induced photodamage, we administered four lotions to the skin of our transgenic mice that included: a sunscreen containing octyl methoxycinnamate and benzophenone-3 with a sun protection factor (SPF) of 15, the UVA filter butyl methoxydibenzoylmethane, the SPF 15 sunscreen and the UVA filter together, and the lotion vehicle alone. Following sunscreen administration, mice received a single psoralen plus ultraviolet A radiation treatment. All sunscreens decreased chloramphenicol acetyl transferase activity with the SPF 15 sunscreen, the UVA filter, and the combination SPF 15 sunscreen and UVA filter, resulting in increasing degrees of protection against psoralen plus ultraviolet A radiation. These results demonstrate that this model functions as a rapid and sensitive model of UVA photodamage for the identification and comparison of compounds that protect against UVA-induced photoaging.