Starting Point Of Sun-induced Skin Cancer Discovered: Molecular 'Hooks' Also Pull Compounds From Marijuana From Bloodstream

"The question at the core of this research was, 'Why does ultraviolet light induce skin cancer?'" said lead researcher Zigang Dong, a professor of cellular and molecular biology and director of the university's Hormel Institute, which supported the study. "The idea is to find an agent that can prevent skin cancers after exposure to the sun."

The receptor molecules are protein structures that are components of cells's outer membranes. Acting like receiving docks, their function is to catch specific compounds from the blood and enable the cells to engulf or otherwise interact with the compounds. Receptors have been identified for many substances, including hormones and other chemical signals that regulate what cells do.

The researchers found that two receptors for cannabinoids also responded to UV light. They made the discovery during a search for the initial interaction between UV light and human skin cells.

The researchers began their search with plant cells because plants must interact with UV light in order to harness its energy for photosynthesis. They concluded that the UV receptors in plants ought to be similar to any found in humans, and, therefore, the genes for the plant and human receptors must also be similar. When they compared plant genes for UV receptors to human genetic material, they found that the human genes for cannabinoid receptors matched.

If cannabinoid receptors are important in the initiation of skin cancer by UV light, then animals that lack the receptors should be relatively protected from the ravages of the light. Working with mouse embryos, the researchers removed the genes for the cannabinoid receptors. They found that the skin of the resulting adult mice, which lacked the receptors, was resistant to the development of UV-induced inflammation and skin tumors called papillomas.

Also, when they exposed cannabinoid receptors to UV light, the receptors changed from an inactive to an active state, indicating they had absorbed and responded to the light.

Why should evolution have produced receptors that respond to both UV light and cannabinoids?

"That we don't know," said Dong.

 The research appears in the May 15 issue of Cancer Research.

The Hormel Institute is a collaborative research unit of the University of Minnesota and Mayo Clinic. The work was supported by the Hormel Foundation and the National Institutes of Health.