Skin pigmentation enhancers.

The highest incidences of cancer are found in the skin, but endogenous pigmentation is associated with markedly reduced risk. Agents that enhance skin pigmentation have the potential to reduce both photodamage and skin cancer incidence. The purpose of this review is to evaluate agents that have the potential to increase skin pigmentation. These include topically applied substances that simulate natural pigmentation: dihydroxyacetone and melanins; and substances that stimulate the natural pigmentation process: psoralens with UVA (PUVA), dimethylsulfoxide (DMSO), L-tyrosine, L-Dopa, lysosomotropic agents, diacylglycerols, thymidine dinucleotides, DNA fragments, melanocyte stimulating hormone (MSH) analogs, 3-isobutyl-1-methylxanthine (IBMX), nitric oxide donors, and bicyclic monoterpene (BMT) diols. These agents are compared with regards to efficacy when administered to melanoma cells, normal human epidermal melanocytes, animal skin, and human skin. In addition, mechanisms of action are reviewed since these may reveal issues related to both efficacy and safety. Both dihydroxyacetone and topically applied melanins are presently available to the consumer, and both of these have been shown to provide some photoprotection. Of the pigmentation stimulators, only PUVA and MSH analogs have been tested extensively on humans, but there are concerns about the safety and side effects of both. At least some of the remaining pigmentation stimulators under development have the potential to safely induce a photoprotective tan.