cysteinyldopa and 5-hydroxy-6-methoxy-2-indolylcarboxylic-acid

Different wavelengths of ultraviolet (UV) radiation elicit different responses in the skin. UVA induces immediate tanning and persistent pigment darkening through oxidation of pre-existing melanin or melanogenic precursors, while UVB induces delayed tanning which takes several days or longer to develop and requires activation of melanocytes. We compared the effects of a 2-week repetitive exposure of human skin to solar-simulated radiation (SSR), UVA or UVB at doses eliciting comparable levels of visible tanning and measured levels of melanins and melanin-related metabolites. Levels of eumelanin and pheomelanin were significantly higher in the order of SSR, UVB, UVA or unexposed control skin. Levels of free 5-S-cysteinyldopa (5SCD) were elevated about 4-fold in SSR- or UVB-exposed skin compared with UVA-exposed or control skin. Levels of protein-bound form of 5SCD tended to be higher in SSR- or UVB-exposed skin than in UVA-exposed or control skin. Total levels of 5-hydroxy-6-methoxyindole-2-carboxylic acid (5H6MI2C) and 6H5MI2C were higher in SSR- than in UVB-exposed or control skin. These results show that SSR is more effective in promoting delayed tanning than UVB radiation alone, suggesting a synergistic effect of UVA radiation. Furthermore, free 5SCD may serve as a good marker of the effect of SSR and UVB.

Topics: Adult; Cysteinyldopa; Dihydroxyphenylalanine; Female; Humans; Indoles; Male; Melanins; Middle Aged; Radiation Dosage; Skin; Skin Pigmentation; Sunlight; Ultraviolet Rays

5-S-Cysteinyldopa (5SCD) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) are formed during biosynthesis of melanins. They are used as indicators of pigment formation and markers of melanoma progression in adults and could possibly be used as markers of activity, growth and even malignant transformation in large pigmented naevi in children. We investigated the urinary excretion of these pigment precursor metabolites from 136 children, 5 to 15 years of age. The mean 5SCD excretion was 38.1 mumol/mol creatinine. A significant age-related decrease from a mean of 60.4 mumol/mol creatinine at 5 years of age to 28.0 mumol/mol creatinine at age 15 was found. In a reference group (29 adults, 20-33 years of age) the mean excretion was 48.9 mumol/mol creatinine. The mean excretion of 6H5MI2C was 42.8 mumol/mol creatinine at 5 years of age and 26.1 mumol/mol creatinine at the age of 15. The mean value for the young adults was 33.4 mumol/mol creatinine. No correlation between the mean excretion of 5SCD and 6H5MI2C was demonstrated. We suggest an upper reference level of 90 mumol/mol creatinine for the excretion of 5SCD in the age group 5-11 years and of 60 mumol/mol creatinine in the age group 13-15 years. Corresponding figures for the indole 6H5MI2C are 70 and 60 mumol/mol creatinine. The establishment of reference values in children will make it possible to use 5SCD and 6H5MI2C measurements as diagnostic tools, indicating growth or malignant transformation in giant melanocytic naevi during childhood.

Topics: Adolescent; Adult; Age Factors; Biomarkers, Tumor; Child; Child, Preschool; Cysteinyldopa; Female; Humans; Indoles; Male; Melanins; Nevus, Pigmented; Sex Factors; Skin Neoplasms

Urinary excretion of 5-S-cysteinyldopa (5-S-CD) has been used as a biochemical marker of melanoma progression. Melanomas produce not only 5-S-CD but also 5,6-dihydroxyindole-2-carboxylic acid (5,6DHI2C) as major intermediates in melanin formation. 5,6DHI2C is then metabolized to the two O-methyl derivatives, 5H6MI2C and 6H5MI2C. The aim of this study was to determine which marker in serum and urine most sensitively reflected the progression of melanoma.. Serum and 24-hour urine samples were collected and assayed serially by high-performance liquid chromatography every 1 to 4 months in 28 patients with primary or recurrent melanomas, for up to 48 months.. Serum concentration and urinary excretion of 5-S-CD and 6H5MI2C in patients with melanoma without metastases were close to those obtained from normal subjects. Metastases developed in 9 of the 28 patients. In seven of these nine patients, serum or urinary 5-S-CD values were elevated before or at the time of clinical detection of visceral metastases. However, serum 5-S-CD was elevated significantly earlier and reflected melanoma progression better than the physical examination and/or laboratory tests, such as scintigraphy and echography. Serum 6H5MI2C values exceeded the normal range shortly before death in three patients, and urinary 6H5MI2C did not increase at any stage in most patients, therefore these metabolites did not reflect progression of disease.. Among the four markers, serum 5-S-CD appears to be the best biochemical marker for the detection of progression of melanotic melanoma, a value of more than 10 nmol/l suggesting the presence of metastasis.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Chromatography, High Pressure Liquid; Cysteinyldopa; Female; Humans; Indoles; Male; Melanoma; Middle Aged; Neoplasm Metastasis; Skin Neoplasms

Urinary 5-S-cysteinyldopa (5-S-CD) has been used as a biochemical marker of melanoma metastasis. A method was developed for determining the eumelanin-related metabolites 5(6)-hydroxy-6(5)-methyoxyindole-2-carboxylic acids (5H6MI2C and 6H5MI2C) in small volumes of serum. We compared these indoles and 5-S-CD regarding the correlation of their production in melanoma, circulation in blood, and excretion in urine, with the weight of highly pigmented, B16 mouse melanoma. An excellent correlation was found between the serum concentration of 5H6MI2C + 6H5MI2C (r = 0.92) and 5-S-CD (r = 0.89) and tumor weight. However, the urinary excretion of 5H6MI2C + 6H5MI2C and 5-S-CD did not show any significant correlation. These results suggest that 5H6MI2C + 6H5MI2C and 5-S-CD in serum may better reflect melanoma progression than those in urine. Furthermore, comparison of the contents of these melanin-related metabolites between highly pigmented and less pigmented B16 melanomas suggests that 5-S-CD may be accumulated in pigmented melanoma by virtue of binding to melanin and that catechol-O-methyltransferase (COMT) may play a regulatory role in pigmentation.

Topics: Animals; Chromatography, High Pressure Liquid; Cysteinyldopa; Indoles; Male; Melanins; Melanoma; Mice; Mice, Inbred C57BL; Skin Neoplasms; Tumor Cells, Cultured

The contents of eumelanin and pheomelanin in the scalp hairs of 4 Japanese patients with total albinism (3 tyrosinase-positive and one negative) and 100 healthy Japanese were measured by the melanin microquantitation method of Ito and Fujita. The urinary 5-S-Cysteinyldopa (5-S-CD) and 5-Hydroxy-6-Methoxyindole-2-Carboxylic acid (5H6MI2C) contents in the 4 albino subjects were also determined. Our findings included that (1) Regardless of ge, black hairs of all the healthy subjects contained phemelanin at a level of about 5% of the total melanin contents. The hair color of the 3 tyrosinase-positive subjects was pale-yellow, and their hairs contained only pheomelanin. The hair color of the one tyrosinase-negative subject was white, and neither eumalanin nor pheomelanin could be detected. (2) Urinary 5H6M12C, an indicator of eumelanin production in the body, could not be detected in either the tyrosinase-positive or tyrosinase-negative subjects, while the urinary 5-S-CD content of the tyrosinase-negative subject was much lower than that of the tyrosinase-positive subjects. These results suggested that the yellow hair color of patients with tyrosinase-positive albinism is attributable to the production of only pheomelanin and that the urinary 5-S-CD content does not necessarily reflect the ability to produce melanin.

Topics: Adolescent; Adult; Albinism, Oculocutaneous; Child; Child, Preschool; Cysteinyldopa; Female; Hair; Humans; Indoles; Japan; Male; Melanins; Middle Aged; Monophenol Monooxygenase; Reference Values

5-S-Cysteinyldopa (5-S-CD), a pheomelanin precursor, has been used as a biochemical marker of melanoma metastasis. Recently, 5-hydroxy-6-methoxyindole-2-carboxylic acid (5H6MI2C), a eumelanin-related metabolite, was shown to reflect well the degree of skin pigmentation. We measured the urinary excretion of 5H6MI2C and 5-S-CD in mice bearing B16 melanoma to determine which of the two markers better reflects the progression of melanoma. The urinary excretion of both 5H6MI2C and 5-S-CD increased rapidly in parallel with the tumour volume. The highest values for the two metabolites in melanoma-bearing mice were three orders of magnitude higher than those in control mice. However, 5H6MI2C had a higher excretion level at the early stage of melanoma progression, while 5-S-CD had a higher excretion level at the later stage.

Topics: Animals; Biomarkers, Tumor; Cysteinyldopa; Dihydroxyphenylalanine; Dopamine; Indoles; Melanins; Melanoma, Experimental; Mice; Mice, Inbred C57BL