The Journal of Nutrition Vol. 127 No. 11 November 1997, pp. 2158-2164
Copyright ©1997 by the American Society for Nutritional Sciences

Dietary L-Histidine Regulates Murine Skin Levels of Trans-Urocanic Acid, an Immune-Regulating Photoreceptor, with an Unanticipated Modulation: Potential Relevance to Skin Cancer

Edward C. De Fabo, Lindsay J. Webber, Edward A. Ulman^*, and Lyle D. Broemeling

Department of Dermatology, The George Washington University Medical Center, Washington, DC 20037; ^* Research Diets, New Brunswick, NJ 08901; and  Biostatistics Center Medical Center Unit, The George Washington University Medical Center, Washington, DC 20037

Solar ultraviolet-B radiation (UVB; 290-320 nm) causes skin cancer and suppresses cell-mediated immunity, preventing the rejection of UV-induced tumors. One mechanism initiating UV suppression involves the trans to cis photoisomerization of urocanic acid (UCA), a histidine derivative found in the stratum corneum. The addition of L-histidine to nonpurified mouse diet has been shown to increase skin trans-UCA levels and sensitivity to UVB immune suppression. Specially formulated L-histidine diets (0.40-64 g/kg) fed to BALB/c mice that were monitored over a 19-wk period resulted in an unexpected modulation of skin trans-UCA. ANOVA revealed a group-time interaction, providing initial evidence that the skin levels of trans-UCA were modulating up and down in all groups except the control group (6.4 g/kg diet). We observed that both high (64 g/kg diet) and low (0.4 g/kg diet) levels of dietary L-histidine resulted in the increase of skin trans-UCA to levels significantly higher than those recorded in the control group. In mice fed these histidine levels, skin trans-UCA increased to between 2.9 and 3.6 nmol/mg skin (64 g/kg diet, over 5 wk; 0.4 g/kg diet, over 8 wk) and then decreased to ~1.69 nmol/mg skin, the base-line level (64 g/kg diet, over 11 wk; 0.4 g/kg diet, over 17 wk). The increase in trans-UCA levels in mice with low L-histidine intake may be the result of protein malnutrition, consistent with weight loss observed in those mice. The modulation of trans-UCA levels in skin by dietary L-histidine has not been previously described; its role in skin cancer development is under investigation.