DakDak Photoaging Technologies, Inc. (DakDak) proposes a Fast-Track Phase I/II program to validate a new mouse model for cutaneous phototoxicology testing for cosmetic products. We have produced genetically hairless transgenic mice expressing the human elastin promoter (EP) linked to the reporter gene chloramphenicol acetyltransferase (CAT), in the Crl: SKH1-hrBR strain that has been standardized for Phototoxicology testing. We previously demonstrated that haired mice expressing EP-CAT showed dose- and time-related responses to UVA and UVB, both in vivo and in vitro. The new hairless EP-CAT mice will make these assays more feasible, allow comparison with the historical database for Cr1:SKHL-hrBR mice, and provide an early quantitative endpoint for UV-induced skin damage, and may lead to an in vitro assay for UV photodamage. The objectives of this Phase I proposal are to select one homozygous transgenic EP-CAT mouse lines from among the 4 we have produced and to optimize the phototoxicology testing parameters with this new line. This will lead to Phase II project., detailed in the accompanying proposal, to validate the use of heterologous EP activation as a surrogate marker for phototoxicology by comparing responses to selected comparitor substances with historical data.
The use of this transgenic mouse model dramatically reduces the time required to perform testing of photoprotective agents or drugs suspected of enhancing phototoxicity, greatly cutting costs and perhaps increasing the number of companies wishing to utilize these services. Our system is the only in vitro system currently used to steady cutaneous photo-aging, thus is available for use in product testing for the large cosmetic market.
|Bernstein, Eric F (2002) Reactive oxygen species activate the human elastin promoter in a transgenic model of cutaneous photoaging. Dermatol Surg 28:132-5|
|Bernstein, E F; Kong, S K; Brown, D B et al. (2001) The nitroxide Tempol affords protection against ultraviolet radiation in a transgenic murine fibroblast culture model of cutaneous photoaging. Exp Dermatol 10:55-61|
|Bernstein, E F (2001) Clinical characteristics of 500 consecutive patients presenting for laser removal of lower extremity spider veins. Dermatol Surg 27:31-3|
|Bernstein, E F; Lee, J; Brown, D B et al. (2001) Glycolic acid treatment increases type I collagen mRNA and hyaluronic acid content of human skin. Dermatol Surg 27:429-33|
|Bernstein, E F (2000) Treatment of a resistant port-wine stain with the 1.5-msec pulse duration, tunable, pulsed dye laser. Dermatol Surg 26:1007-9|