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5-Methyltetrahydrofolate inhibits photosensitization reactions and strand breaks in DNA

Tal Offer^*,, Bruce N. Ames^*, Steven W. Bailey, Elizabeth A. Sabens, Mamoru Nozawa and June E. Ayling^,1

^* Nutrition and Metabolism Center, CHORI, Oakland, California; and

Department of Pharmacology, University of South Alabama, Mobile, Alabama, USA

¹Correspondence: Department of Pharmacology Rm. 3370, MSB, 307 North University Blvd., University of South Alabama, Mobile, AL 36688. E-mail: jayling{at}jaguar1.usouthal.edu

The known functions of folate are to support one-carbon metabolism and to serve as photoreceptors for cryptochromes and photolyases. We demonstrate that 5-methyltetrahydrofolate (5-MTHF, the predominant folate in plasma) is also a potent, near diffusion limited, scavenger of singlet oxygen and quencher of excited photosensitizers. Both pathways result in decomposition of 5-MTHF, although ascorbate can protect against this loss. In the absence of photosensitizers, 5-MTHF is directly decomposed only very slowly by UVA or UVB. Although synthetic folic acid can promote DNA damage by UVA, submicromolar 5-MTHF inhibits photosensitization-induced strand breaks. These observations suggest a new role for reduced folate in protection from ultraviolet damage and have bearing on the hypothesis that folate photodegradation influenced the evolution of human skin color.—Offer, T., Ames, B. N., Bailey, S. W., Sabens, E. A., Nozawa, M., Ayling, J. E. 5-Methyltetrahydrofolate inhibits photosensitization reactions and strand breaks in DNA.

Key Words: folate • folic acid • ultraviolet radiation • singlet oxygen • supercoiled DNA