title: Dietary L-histidine regulates murine skin levels of trans-urocanic acid, an immune-regulating photoreceptor, with an unanticipated modulation: potential relevance to skin cancer.
abstract: 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 approximately 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.
authors.affiliation: Department of Dermatology, The George Washington University Medical Center, Washington, DC 20037, USA.
authors.forename: E C
authors.initials: EC
authors.lastname: De Fabo
authors.forename: L J
authors.initials: LJ
authors.lastname: Webber
authors.forename: E A
authors.initials: EA
authors.lastname: Ulman
authors.forename: L D
authors.initials: LD
authors.lastname: Broemeling
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002851:Chromatography, High Pressure Liquid; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005260:Female; D006639:Histidine / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D007165:Immunosuppression Therapy; D007536:Isomerism; D016014:Linear Models; D051379:Mice; D008807:Mice, Inbred BALB C; D010786:Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism*; D012867:Skin / Q000737:chemistry* / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D014466:Ultraviolet Rays; D014560:Urocanic Acid / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism
chemical_list: D006639:Histidine; D014560:Urocanic Acid