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PubMed2002

Quantitative relationships between pigment-related mRNA and biochemical melanoma markers in melanoma cell lines.

The use of reverse transcription polymerase chain reaction (RT-PCR) analysis of melanoma-specific transcripts for the identification of circulating melanoma cells has shown very variable results in different studies on melanoma patients. We have therefore developed quantitative methods to study both analytical and biological variations as possible causes of this phenomenon. Pigment-related and S-100 beta transcripts were quantified in 12 different melanoma cell lines and related to the amounts of 5-S-cysteinyldopa, pigment and S-100B protein. A real-time PCR method was used and the results were expressed as absolute number of transcripts per cell. Tyrosinase, tyrosinase-related protein (TRP)-1, TRP-2 and MART-1/Melan-A mRNA varied from undetectable (< 10(-4) transcripts/cell) to 10(3) transcripts/cell, i.e. by a factor > 10(7) in the different cell lines. S-100 beta mRNA varied from 2.8 to 165 transcripts/cell, i.e. by a factor of 60. Tyrosinase, TRP-1 and TRP-2 mRNA correlated significantly with the amount of 5-S-cysteinyldopa, an intermediate pigment metabolite (P < 0.001, P < 0.001 and P < 0.01, respectively). The amount of S-100 beta mRNA correlated significantly with the amount of S-100B protein (P < 0.001). No cross-correlations were seen between the pigment-related and S-100-related analytes. We conclude that one reason behind the negative results of RT-PCR measurement of pigment-related mRNA may be that these transcripts are not always expressed in the particular cells present in the patient's blood. Furthermore, variation in the expression of the order of 10(7) must have great impact on the diagnostic sensitivity. Measurement of S-100 beta mRNA would be more sensitive, but the use of this transcript is hampered by its presence in the blood cells.

Antigens, Neoplasm↗
PubMed1986

Effects of melanin-induced free radicals on the isolated rat peritoneal mast cells.

Pheomelanin from human red hair (RHM) produces considerably more cellular damage in Ehrlich ascites carcinoma cells when subjected to radiations of wavelength 320-700 nm than eumelanin from black hair (BHM). Irradiation of RHM generated large amounts of superoxide while BHM did not produce detectable amounts of superoxide. The present investigations describe the effects of irradiation of mast cells in the presence of various natural and synthetic melanins. Irradiation of mast cells in the presence of RHM and red hair melanoprotein released large amounts of histamine while BHM and synthetic melanins prepared from dopa, cysteinyldopa, or a mixture of dopa and cysteinyldopa did not release histamine. The release of histamine at lower concentrations of RHM was not accompanied by the release of 51Cr from chromium-loaded cells, suggesting that this release was of noncytotoxic nature. On the other hand, the release of histamine at higher concentrations of RHM was due to cell lysis since both histamine and cytoplasmic marker 51Cr were released to the same extent. The release evoked by large concentration RHM was not inhibited by superoxide dismutase or catalase. This suggests that the cell lysis under these conditions was not due to H2O2 or O-2. The finding that mast cells release histamine when irradiated in the presence of RHM suggests that the immediate and late-phase reactions seen in sunburn may in part be due to the release of mediators from these cells.

Animals↗
PubMed1987

Inhibition of melanization in human melanoma cells by a serotonin uptake inhibitor.

Significant levels of intracellular catecholamines were found in a human melanoma cell line and were enhanced by increasing the extracellular tyrosine concentration. Intracellular dopa, 5-cysteinyldopa, tyrosinase, and melanin also rose under these conditions. 5-HT (serotonin) was synthesized by the melanoma cells but further study was hindered by the high level of 5-HT in fetal calf serum. A 5-HT uptake antagonist, DU 24565 (6-nitroquipazine), was employed as an alternative method for studying 5-HT action. This compound, which in contrast to tunicamycin had no inhibitory effects on cell proliferation or tyrosinase activity, strongly inhibited melanization and decreased the levels of dopa, 5-cysteinyldopa, dopamine, noradrenaline, adrenaline, and 3,4-dihydroxyphenylacetic acid. DU 24565 had little effect on 5-HT or tyrosine accumulation in these cells but suppressed the uptake of extracellular dopa. The results show that human melanoma cells synthesize a wide range of biogenic amines in culture and suggest a new approach to regulating intracellular levels of dopa and of a variety of dopa products.

Catecholamines↗
PubMed1995

Current update and trends in melanin pigmentation and melanin biology.

Certain aspects of current progress in melanin biology and its possible clinical relevances are reviewed with emphasis on some of our recent research activities. The important aspects discussed are (a) the biological properties of melanin pigments and their relevance to biological functions, (b) functional interaction of melanogenic/melanogenesis-associated genes in melanin biosynthesis process (melanogenesis, and (c) the targeting of proteins involved in melanogenesis and assembly by melanosomal proteins. Upon exposure to UV light radiation (UVR), melanin pigments revealed two distinct photobiological reactions, i.e. photoprotective and phototoxic reactions. The precursor intermediate of brown-black eumelanin, 5-6-dihydroxyindole, appears to possess the most potent photoprotective (antioxidant) property. Eumelanin pigment also had some antioxidant property. Similarly, yellow-red pheomelanin and its precursor intermediate, 5-S-cysteinyldopa also revealed some antioxidant property, but they became prooxidant in the presence of the ferric iron upon exposure to UVR. Melanosomes are known to possess several metal ions including Fe2+, Fe3+, Cu2+ and Zn2+. In addition, upon exposure to UV-light, there is an increase in ferric/ferrous iron in the skin. Therefore, in the in vivo system, pheomelanin intermediate, 5-S-cysteinyldopa, may show significant prooxidant property in conjunction with metal ions (e.g. Fe2+, Fe3+). When atypical moles (previously called dysplastic nevi) were analysed chemically for quantitative and qualitative properties of melanin pigment, they revealed a high ratio of pheomelanin/eumelanin content. This finding may partly explain our clinical observation that these moles are frequently the precursors of malignant melanoma and that the intermittent heavy exposure of UVR can be the major direct cause of their transformation. How, then, the melanosomal compartment, where active new melanin synthesis occurs after exposure to UVR, is protected from the cytotoxicity of melanin precursor intermediates. To study this question, two major experiments were conducted; (a) expression of melanogenesis-associated genes upon exposure of melanocytes to UVR and (b) transfection of cDNAs from the melanogenesis-associated genes. There was coordinated gene expression (mRNA) of tyrosinase and tyrosinase-related protein, TRP-1 and this coordinated gene expression was also accompanied by the upregulation of LAMP-1 (lysosome-associated membrane protein-1). Furthermore, human tyrosinase and TRP-1 mRNAs were expressed successfully in individual transfectants or co-transfectants of cDNAs from the two genes. Co-transfectants of human tyrosinase and TRP-1 cDNAs produced many lysosomal granules and melanin-containing granules, melanosomes. LAMP-1 gene was upregulated simultaneously in co-transfectants of tyrosinase and TRP-1, but not in individual transfectants of the two genes.(ABSTRACT TRUNCATED AT 400 WORDS)

Forecasting↗
PubMed1979

A new approach to the differential diagnosis of human malignant melanomas.

In an attempt to improve the diagnosis of melanotic tumors, we have compared the diagnosis obtained by histological examination of 216 skin tumors and their metastases with that obtained by using a conjunction of four techniques: tissue culture, cytoenzymology, in situ electron microscopy and 5-S-cysteinyldopa (5-S-CD) assay. In 46 cases the final diagnosis as determined by one or more of these tests differed from the initial histological diagnosis, but was confirmed by repeat histological examination. We conclude that this method presents a valuable new approach to the differential diagnosis of human malignant melanoma.

Adolescent↗
PubMed1994

Evaluation of melanin-related metabolites as markers of melanoma progression.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Adult↗
PubMed1977

Fluorescence histochemical demonstration of dopa thioethers by condensation with gaseous formaldehyde.

The usefulness of the formaldehyde (FA) and glyoxylic acid (GA) methods for the fluorescence histochemical demonstration of dopa thioethers has been tested using protein droplet models. Similar fluorescence intensities were recorded from these compounds after either FA or GA treatment. Cysteinyldopa gave a high fluorescence yield similar to that obtained from dopamine and dopa in the FA reaction, whereas gluatitodopa showed a lower, although clearly visible fluorescence. Since the FA method seemed to be the most useful one for demonstration of catechol thioethers, the FA-induced fluorophores of these compounds were further characterized by microspectrofluorometry. The spectral characteristics of the thioether fluorophores (excitation maxima at 420 nm and emission maxima at 480-485 nm) distinguish these substances from dopa and other compounds fluorogenic in the Falck-Hillarp method. Dopa thioethers are proposed to form fluorophores with FA in a manner analogous to that of the primary catecholamines i.e. via low-fluorescent tetrahydroisoquinolines, along two different pathways, to strongly fluorescent 3,4-dihydroisoquinolines and 2-methyl-dihydroisoquinolinium compounds. These dihydroisoquinolines are in a pH-dependent tautomeric equilbrium with their quinoidal forms as reflected by a characteristic spectral shift upon acidification. The results of this study provide the guide-lines for the characterization of fluorogenic compounds in pigment-forming cells.

Cysteinyldopa↗
PubMed1986

Interaction of radicals from water radiolysis with melanin.

Melanins are considered to be natural photoprotectors in the melanocytes and keratinocytes of the skin. These pigments have also been suggested to play an important role in protection of melanin-containing cells against ionising radiation. Various mechanisms have been proposed to explain the protective role of melanin which invoke the radical scavenging properties of the polymer. In the present work the reactions of melanins with radicals generated in aqueous media by pulse radiolysis have been studied. Time-resolved changes in absorbance of the melanin or the radical species were recorded at selected wavelengths. Experiments were carried out on synthetic dopa- and 5-S-cysteinyldopa-melanins and a natural melanin in phosphate buffer (pH 7.4). Under the conditions employed, melanin reacted predominantly with either oxidising (OH., N3.) or reducing (eaq-, CO2-) species. We were also able to monitor the interaction of melanin with superoxide radical, which was reducing in this case. Detailed analysis of transient changes in melanin absorbance, detected at different wavelengths, was demonstrated to be a convenient method for studying redox processes of this substance, as shown by model experiments using ferricyanide and dithionite as oxidising and reducing agents, respectively. Among the radicals studied, OH. exhibited the strongest reactivity with melanins. Apparent rate constants for the reactions of radicals with autoxidative dopa-melanin (1.5 X 10(9) M-1 X s-1, 2.6 X 10(8) M-1 X s-1, 1.8 X 10(8) M-1 X s-1, 5 X 10(5) M-1 X s-1, 10(6)-10(7) M-1 X s-1 for OH., eaq-, N.3. O2- and CO2-, respectively) are reported. The reactivity of melanins with radicals from water radiolysis and their effect on pigment properties are discussed in terms of the structure and possible biological role of the pigments.

Carbon Dioxide↗
PubMed1997

Diffusible melanin-related metabolites are potent inhibitors of lipid peroxidation.

Although it has long been known that epidermal melanocytes produce and excrete a number of melanin-related metabolites, including 5.6-dihydroxyindole (DHI), 5,6-dihydroxyindole-2-carboxylic acid (DHICA), and 5-S-cysteinyldopa (CD), the possible functional significance of these compounds has been so far largely overlooked. We report now evidence that DHI, DHICA and CD exert potent inhibitory effects in different in vitro models of lipid peroxidation. The compounds, at 100 microM concentration, substantially decreased malondialdehyde (MDA) formation by lipid peroxidation in rat brain cortex homogenates. At 1.2 microM concentration, DHI proved as effective as alpha-tocopherol (alpha-T), one of the most potent endogenous antioxidants, in suppressing azo-induced peroxidation of linoleic acid in phosphate buffer (pH 7.4), containing 0.10 M SDS, whereas CD and DHICA at the same concentration were less active. DHI, CD and DHICA (all in the range 25 microM-0.5 mM) were also found to inhibit Fe (II)/EDTA-induced oxidation of 0.5 mM arachidonic acid at pH 7.4, as well as MDA formation by iron-promoted degradation of 0.5 mM 15-hydroperoxy-5,8,11, 13-eicosatetraenoic acid (15-HPETE). In both cases the inhibitory effects were much greater than those of ascorbic acid and glutathione. These results point to melanin precursors as a novel class of biological antioxidants which may contribute to defense mechanisms against oxidative injury in human skin.

Animals↗
PubMed1985

Brown oculocutaneous albinism. Clinical, ophthalmological, and biochemical characterization.

The clinical, ophthalmological, and biochemical characteristics of a 28-year-old black woman with brown oculocutaneous albinism were determined. Hair color was medium brown and skin color was light brown, and a faint tan developed with sun exposure. The irides were light brown in the central one-third, blue-gray in the peripheral two-thirds, and showed punctate and radial translucency. Visual acuity was 20/60 in the right eye and 20/100 in the left eye. There was a moderate pendular nystagmus, and previous surgeries had corrected an exotropia. The foveal reflex was muted, and the retinal pigment was reduced. Hairbulb tyrosinase activity was 1.75 pmoles/120 min/hairbulb, hairbulb glutathione content 0.83 nmoles/hairbulb, and urine excretion of 5-S-cysteinyldopa 174.9 ng/mg creatinine. Electron microscopy of hairbulb and skin melanocytes showed arrested melanosomal development. These findings suggest that there is a partial block in the distal eumelanin pathway in this form of albinism. The ophthalmological characteristics of six additional cases of this form of albinism are also presented.

Adult↗
PubMed2000

New regulatory mechanisms in the biosynthesis of pheomelanins: rearrangement vs. redox exchange reaction routes of a transient 2H-1, 4-benzothiazine-o-quinonimine intermediate.

Pheomelanins, the typical epidermal pigments of red haired, Celtic-type Caucasians, arise from oxidative cyclization of cysteinyldopas, mainly the 5-S-isomer CD, via 1,4-benzothiazines. However, the mechanism and the relative yields of formation of these intermediates have remained poorly defined. We have now examined the course of the oxidation of CD at physiological pHs, under different reaction conditions. Surprisingly, a consumption of CD far exceeding the stoichiometry of the oxidant was observed at low oxidant-to-substrate ratios, low temperatures and high substrate concentrations. The yields of the 3,4-dihydro-1,4-benzothiazine-3-carboxylic acid DHBCA vs. the non-carboxylated analogue DHB in the oxidation mixture, after NaBH4 reduction, were also found to depend markedly on the reaction conditions. Based on these and other results, a reaction scheme is proposed involving a transient o-quinonimine generated by oxidative cyclization of CD to which three different paths are offered, namely redox exchange with CD to give DHBCA (path A) or intramolecular rearrangement with (path B) or without (path C) decarboxylation, leading to the benzothiazine BTZ and the 3-carboxy analogue BTZCA, respectively. The relative operation of path A vs. path C was assessed by deuterium labeling experiments. These findings point to new mechanisms of regulation of the initial steps of pheomelanogenesis, bearing significant implications on the structure of the final pigment.

Buffers↗
PubMed2003

Use of serum 5-S-CD and S-100B protein levels to monitor the clinical course of malignant melanoma.

5-S-Cysteinyldopa (5-S-CD) is a precursor of pheomelanin. S-100B protein is a low molecular weight, acidic, calcium binding, cytoplasmic protein. In this study, the concentration changes of serum 5-S-CD and S-100B protein in melanomas of all stages were examined in parallel and patients were monitored during and after treatment. Serum samples were taken from 478 melanoma patients on 1924 occasions. Of these, 180 cases were regularly monitored. Concentrations of 5-S-CD were determined by high performance liquid chromatography (HPLC), S-100B protein by immunoluminometric assay. The mean/median concentrations of 5-S-CD and S-100B protein in Stage I, II and III patients and in the control group ranged around the normal level. In Stage IV patients, 58.4/50.6% sensitivity, 100% specificity and 100/86.6% positive predictive values were obtained concerning S-100B protein and 5-S-CD, respectively. Recurrence was observed in 57/180 of the regularly monitored patients in Stages I, II and III. In 10/57 (17.5%) of these patients suffering from any type of disease progression increases in both marker levels preceded the detection of metastasis by conventional methods. We can confirm that changes in both marker concentrations correlated with the stages of the patient. The markers are most sensitive in Stage IV patients and also have a high specificity in these patients. In Stage IV melanoma patients, 5-S-CD and S-100B protein levels are independent significant prognostic factors. In almost one fifth of patients both marker levels increased before the detection of metastatic disease with other appropriate, routinely scheduled investigations. This study suggests that serial serum marker measurements in the management and follow-up of melanoma patients should be examined further.

Adolescent↗
PubMed2001

Pulse radiolysis studies of ortho-quinone chemistry relevant to melanogenesis.

The contributions of pulse radiolysis towards characterisation of unstable ortho-quinones relevant to melanogenesis are reviewed. The quinones discussed include dopaquinone, the precursor of both eumelanogenesis and phaeomelanogenesis, and 5-S-cysteinyldopaquinone, an early component of the phaeomelanogenic pathway. Redox exchange between dopaquinone and 5-S-cysteinyldopa is shown to be a determinant of the balance between eumelanogenesis and phaeomelanogenesis. Ortho-quinones resulting from the oxidation of tertiary N,N-dialkylcatecholamines cyclise to redox-inactive betaines which fail to autoactivate tyrosinase. This is consistent with the dopa detected during melanogenesis catalysed by tyrosinase being formed indirectly by a combination of dopaquinone intramolecular reductive addition to form leucodopachrome (cyclodopa), followed by redox exchange between remaining dopaquinone and leucodopachrome. Rapid tautomerism of the ortho-quinone of 4-cyanomethylcatechol to a redox-inactive quinomethane likewise inhibits tyrosinase autoactivation. The incorporation of trihydric phenol moieties in melanin is modelled by the reactions of several ortho-quinones with phloroglucinol, which itself is not directly oxidised by tyrosinase due to the meta-positioning of the hydroxyl groups. The importance of a susceptibility towards nucleophilic attack as well as a propensity to undergo redox-exchange, in the chemistry of melanogenic ortho-quinones, is emphasised.

Benzoquinones↗
PubMed2006

Radiative relaxation in synthetic pheomelanin.

We report a detailed photoluminescence study of cysteinyldopa-melanin (CDM), the synthetic analogue of pheomelanin. Emission spectra are shown to be a far more sensitive probe of CDM's spectroscopic behavior than are absorption spectra. Although CDM and dopa-melanin (DM, the synthetic analogue of eumelanin) have very similar absorption spectra, we find that they have very different excitation and emission characteristics; CDM has two distinct photoluminescence peaks that do not shift with excitation wavelength. Additionally, our data suggest that the radiative quantum yield of CDM is excitation energy dependent, an unusual property among biomolecules that is indicative of a chemically disordered system. Finally, we find that the radiative quantum yield for CDM is approximately 0.2%, twice that of DM, although still extremely low. This means that 99.8% of the energy absorbed by CDM is dissipated via nonradiative pathways, consistent with its role as a pigmentary photoprotectant.

Cysteinyldopa↗
PubMed1977

A new amino acid, 3-(2,5-SS-dicysteinyl-3,4-dihydroxyphenyl)alanine, from the tapetum lucidum of the gar (Lepisosteidae) and its enzymic synthesis.

The tapetum lucidum of the alligator gar Lepisosteus was shown by t.l.c. to contain a new phenolic amino acid, which is apparently a major constituent of the reflecting material. It was isolated in a yield of 0.5 mg/eye and its physical and chemical characteristics, especially reductive hydrolysis with hydriodic acid giving dopa (3,4-dihydroxyphenylalanine) and cysteine, suggested that it might to SS-dicysteinyldopa. Tyrosinase oxidation of L-dopa in the presence of an excess of L-cysteine yielded, in addition to known 5- and 2-S-cysteinyldopa, the same amino acid as that isolated from the eye of the gar, thus confirming the gross structure. The position of the two cysteine residues was established by the fact that tyrosinase oxidation of catechol and cyteine gave 3-S-cysteinylcatechol and 3,6-SS-dicysteinylcatechol. The natural amino acid is therefore formulated as 3-(2,5-SS-dicysteinyl-3,4-dihydroxyphenyl)alanine (2,5-SS-dicysteinyldopa), which may be formed by two consecutive additions of cysteine, first to dopaquinone and then to 5-S-cysteinyldopaquinone. The enzymic synthesis of 2,5-SS-dicysteinyldopa in vitro suggests that it may also be involved in the biosynthesis of phaeomelanin.

Animals↗
PubMed2003

Changes in the proliferation and differentiation of neonatal mouse pink-eyed dilution melanocytes in the presence of excess tyrosine.

Changes in the proliferation and differentiation of epidermal melanocytes derived from newborn mice wild-type at the pink-eyed dilution (p) locus (P/P) and from congenic mice mutant at that locus (p/p) were investigated in serum-free primary culture, with or without the addition of L-Tyr. Incubation with added L-Tyr inhibited the proliferation of P/P melanocytes in a concentration-dependent manner and inhibition was gradually augmented as the donor mice aged. In contrast, L-Tyr stimulated the proliferation of p/p melanoblasts-melanocytes derived from 0.5-day-old mice, but inhibited their proliferation when derived from 3.5- or 7.5-day-old mice. L-Tyr stimulated the differentiation of P/P melanocytes. However, almost all cells were undifferentiated melanoblasts in control cultures derived from 0.5-, 3.5- and 7.5-day-old p/p mice, but L-Tyr induced their differentiation as the age of the donor mice advanced. The content of the eumelanin marker, pyrrole-2,3,5-tricarboxylic acid as well as the pheomelanin marker, 4-amino-3-hydroxyphenylalanine in p/p melanocytes was greatly reduced compared with P/P melanocytes. However, the contents of eumelanin and its precursor, 5,6-dihydroxyindole-2-carboxylic acid, as well as the contents of pheomelanin and its precursor, 5-S-cysteinyldopa in culture media from p/p melanocytes were similar to those of P/P melanocytes at all ages tested. L-Tyr increased the content of eumelanin and pheomelanin two- to threefold in cultured cells and media derived from 0.5-, 3.5- and 7.5-day-old mice. These results suggest that the proliferation of p/p melanoblasts-melanocytes is stimulated by L-Tyr, and that the differentiation of melanocytes is induced by L-Tyr as the age of the donor mice advanced, although eumelanin and pheomelanin fail to accumulate in p/p melanocytes and are released from them at all ages of skin development.

Animals↗
PubMed2004

Pheomelanin production in the epidermis from newborn agouti mice is induced by the expression of the agouti gene in the dermis.

The present study was designed to clarify the role of the agouti gene in the regulation of the proliferation and differentiation of mouse epidermal melanocytes using serum-free primary culture of epidermal melanocytes from 0.5-d-old black (a/a; C57BL/10JHir) mice and congenic, agouti (A/A; C57BL/10JHir-A/A) mice. There was no significant difference in the proliferation or differentiation of melanocytes between a/a and A/A mice. However, the content of pheomelanin in culture media from A/A melanocytes was increased by L-tyrosine compared with a/a melanocytes. In addition, the content of the pheomelanin precursor, 5-S-cysteinyldopa, in culture media from A/A melanocytes was dramatically increased by L-tyrosine. Moreover, pheomelanin content in the epidermis from 3.5- and 5.5-d-old A/A mice was much higher than in a/a mice. Analysis of the A gene using reverse transcription-polymerase chain reaction revealed that cultured keratinocytes and melanocytes do not express the A gene. Moreover, the A gene was expressed in the A/A dermis of 0.5-, 3.5- and 5.5-d-old mice, but not in the a/a dermis nor in the A/A or a/a epidermis. These results suggest that A/A epidermal melanoblasts are influenced by the A gene from the dermis of neonatal mice, and are capable of synthesizing pheomelanin in the culture. Pheomelanin production in the epidermis from 3.5- and 5.5-d-old A/A mice may be induced by the expression of the agouti gene in the dermis.

Agouti Signaling Protein↗
PubMed2006

Evaluation of melanin-related metabolites as markers of solar ultraviolet-B radiation.

Ultraviolet-B (UVB) radiation due sunlight can result in sunburns and/or suntans. Sunburn occurs only several hours after solar UVB radiation, while a suntan requires several days to several weeks to develop. In the present study, we measured serum and urine levels of melanin-related metabolites, 5-S-cysteinyldopa (5-S-CD) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C), in nine subjects exposed to normal sunlight over the course of 12 months. We collected samples in the middle of each month and examined the variation of the markers, the correlation between them, and their correlation with solar UVB radiation. Those markers exhibited a seasonal variation with lower values in the winter and higher values in the summer. Levels of 5-S-CD and 6H5MI2C in the serum showed 48% and 54% increases in the summer compared with those in the winter, respectively. Comparison of 5-S-CD in the serum and urine showed the highest correlation (r2 = 0.344), followed by the pair of 5-S-CD and 6H5MI2C in the serum. Levels of 5-S-CD in the serum showed the highest correlation (r2 = 0.729) with the mean solar UVB radiation during the first 10 d of the month, while 6H5MI2C in the serum was highly correlated (r2 = 0.483) with solar UVB radiation during the previous month. Levels of 5-S-CD and 6H5MI2C in the serum appear to reflect the degrees of skin injury and pigmentation in the skin, respectively.

Adult↗