DIETARY L-HISTIDINE REGULATES MURINE SKIN LEVELS OF TRANS-UROCANIC ACID, AN IMMUNE-REGULATING PHOTORECEPTOR, WITH AN UNANTICIPATED MODULATION - POTENTIAL RELEVANCE TO SKIN-CANCER

Solar ultraviolet-B radiation (UVB; 290-320 nm) causes skin cancer and suppresses cell-mediated immunity, preventing the rejection of UV-ind uced tumors, One mechanism initiating UV suppression involves the tran s to cis photoisomerization of urocanic acid (UCA), a histidine deriva tive found in the stratum corneum, The addition of L-histidine to nonp urified mouse diet has been shown to increase skin trans-UCA levels an d sensitivity to UVB immune suppression. Specially formulated L-histid ine 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 th at the skin levels of trans-UCA were modulating up and down in all gro ups except the control group (6.4 g/kg diet). We observed that both hi gh (64 g/kg diet) and low (0.4 g/kg diet) levels of dietary L-histidin e resulted in the increase of skin trans-UCA to levels significantly h igher than those recorded in the control group, In mice fed these hist idine 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 decr eased to similar to 1.69 nmol/mg skin, the base-line level (64 g/kg di et, 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 protei n malnutrition, consistent with weight loss observed in those mice. Th e modulation of trans-UCA levels in skin by dietary L-histidine has no t been previously described; its role in skin cancer development is un der investigation.