UV radiation generates reactive oxygen species in the skin that promote photoaging and carcinogenesis. Manganese superoxide dismutase (MnSOD) is an endogenous mitochondrial anti-oxidant enzyme that protects cells from oxidative damage by the highly reactive superoxide molecule. By regulating the homeostasis of oxygen radicals within the mitochondria, MnSoD critically participates in the control of senescence and tumor generation. Thus, MnSOD is an important component in the cellular defense against UV radiation-induced tissue damage and there is a need to identify a safe, easy method to induce and maintain elevated levels of MnSOD in order to exert this protective effect.

Dr. David Grdina and colleagues at the University of Chicago have identified a class of aminothiol agents including WR1065, the free thiol form of amifostine, that can induce elevated manganese superoxide dismutase (MnSOD) in tissue. They have demonstrated that this increased- mitochondrial localized- antioxidant activity results in enhanced resistance to the damaging effects of radiation-induced ROS on both genomic integrity and cellular function. Furthermore, they have shown that this elevated level of protection can be achieved and maintained over a prolonged period of time by daily or every other day dosing. As these phosphorothioates have been previously demonstrated to be efficacious through topical administration, they represent an effective and safe product with which to protect against dermal mutations and their long term consequences induced by exposure to UV-radiation.

File Number: UCHI 0489 & UCHI 0704 

Web site: http://www.radonc.uchicago.edu/typea/fac_dgrdin...