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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This work studies the phenotype changes, relating to pigment expression, of a human melanoma cell line. The phenotypic instabilities and proliferation rates are correlated with the production and release in the cell culture medium of active oxygen species and melanin synthesis intermediates. The proliferation rates versus L-tyrosine concentration in the culture media are investigated: a decrease is found when high L-tyrosine is added to the medium. This would be consistent with the release of cytotoxic and/or genotoxic species by melanoma cells. The morphology of melanoma melanosomes is coherent with the leakage of cytotoxic and genotoxic species produced during melanin synthesis.
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PMID:Cyto-genotoxic species leakage within human melanoma melanosomes. Molecular-morphological correlations. 806 41

B-16 mouse melanoma melanosomes contain two forms of tyrosinase that can be resolved by SDS/PAGE. These forms interact to different extents with the ion-exchanger DEAE-Sephadex and with hydroxyapatite, and have different affinity for the melanosomal membrane and/or the intraorganular matrix. After partial purification and complete separation of the two tyrosinases, several kinetic parameters were analyzed. The form of lower electrophoretic mobility displayed a higher Km for 3,4-dihydroxy-L-phenylalanine (L-dopa) and L-tyrosine, an absolute requirement for the cofactor L-dopa in its tyrosine hydroxylase activity, and a lower ratio of tyrosine hydroxylation to Dopa oxidation. The form of higher electrophoretic mobility displayed lower values of Km for both substrates and was able to exhibit tyrosine hydroxylase activity after a lag period even in the absence of L-dopa. Both forms were stereospecific for the L isomers and sensitive to the specific tyrosinase inhibitor 2-phenylthiourea. These forms do not appear to result from different degrees of glycosylation, nor from limited proteolysis and are also present in the microsomal fraction of B16 mouse melanoma. They might correspond to different gene products, most likely derived from the b and c loci.
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PMID:Tyrosinase isoenzymes in mammalian melanocytes. 1. Biochemical characterization of two melanosomal tyrosinases from B16 mouse melanoma. 822 98

In a previous study an apparent discrepancy was found between the radiobiological hypoxic fraction of tumours and the tumour oxygenation: the lowest percentage of low pO2 values was observed in the most hypoxic tumour, a heavily pigmented melanoma Na11+. This report describes a similar study with two other less pigmented melanomas. The influence of melanin on pO2 readings was also studied using synthetic melanin and L-tyrosine. Tumour oxygenation was measured using the KIMOC 6650 histograph, apparent pO2 was also measured in the calibration chamber in a buffer containing melanin or L-Tyr at three pHs (6.5, 7.0, 7.5) and bubbled with three different oxygen concentrations (0.2, 2.0, 20.9%). The proportion of hypoxic cells, measured by an in vivo/in vitro colony assay, was 58% for Na11+, 30% for Be11 and 51% for Ma11 tumours. The melanin content (microgram/10(6) cells) was 6.5 (Na11+), 2.0 (Be11), and 4.3 (Ma11). The percentages of radiobiologically hypoxic cells and low pO2 reading values (<2 mmHg) were inversely correlated, contrary to what was expected. In buffer, the pO2 values increased significantly with the melanin concentration: the lower the oxygen concentration, the greater was the increase in pO2. The pO2 readings values increased to a lesser extent with L-Tyr concentration. These results indicate that clinical determination of pO2 in melanoma tumours requires careful attention.
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PMID:Influence of melanin on pO2 measurement in vitro and in vivo. 860 57

Tyrosinase isolated from cultured human melanoma cells was studied for tyrosine oxygenation activity. L-Tyrosine and D-tyrosine were used as substrates and dopa was measured with HPLC and electrochemical detection as the product of oxygenation. Incubations were performed in the presence or absence of dopamine as co-substrate. Oxygenation of L-tyrosine occurred only in the presence of dopamine as co-substrate. No oxygenation of D-tyrosine was found, and we conclude that human tyrosinase is characterised by exclusive specificity for the L-isomer of tyrosine in its oxygenase function. It has recently been suggested that superoxide anion is a preferential oxygen substrate for human tyrosinase. Incubations were therefore performed with L- and D-tyrosine, human tyrosine, and xanthine/xanthine oxidase in the system, generating superoxide anion and hydrogen peroxide. Considerable formation of dopa was observed, but the quantity was the same irrespective of whether D-tyrosine or L-tyrosine was used as the substrate. Furthermore, formation of dopa occurred in a xanthine/xanthine oxidase system when bovine serum albumin (BSA) was substituted for tyrosinase. Our results provide no evidence that superoxide anion is an oxygen substrate for human tyrosinase. In the incubate containing xanthine/xanthine oxidase, catalase completely inhibited dopa formation, and superoxide dismutase and mannitol each strongly inhibited dopa formation. The results are compatible with hydroxyl radicals being responsible for the formation of dopa, since such radicals may be secondarily formed in the presence of superoxide anion and hydrogen peroxide.
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PMID:Enzymatic and non-enzymatic oxygenation of tyrosine. 885 72

Characterization of genes expressed in normal cells and decreased in their malignant counterparts is important for detecting candidate tumor suppressor genes. We have now used comparative differential display of MRNAs from B16 melanoma and matched syngeneic normal melanocytes to detect a G0A gene expressed preferentially in resting G0 melanocytes compared to proliferating cells. Cloning and sequencing revealed no homology of G0A in the GenBank Database, suggesting that this is a new gene. Northern blot analysis with the cloned probe, confirmed about a five-fold higher expression in normal melanocytes compared to melanoma. Up-regulation of this gene was not detected by L-tyrosine induction of B16 melanoma terminal differentiation, but was seen in these cells, when exposed to the radiation sensitizer bromodeoxyuridine and subsequent UV radiation. Our differential expression data suggest that the G0A gene is important for melanocytic growth control and for the response of melanoma cells to radiation sensitizers.
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PMID:PCR-mediated differential display and cloning of a melanocyte gene decreased in malignant melanoma and up-regulated with sensitization to DNA damage. 892 17

This paper presents evidence that L-tyrosine oxidation products and 5,6-dihydroxyindole, an intermediate of melanin synthesis bind to and modify DNA structure, as tested by extracting cell DNA, using topoisomerase I and denaturation assays. When supercoiled plasmid pCU18 or pBR322 DNAs are treated with 5,6-dihydroxyindole the supercoiled species disappear and are converted to species less mobile in a gel retardation test with respect to relaxed DNA, 5,6-Dihydroxyindole causes an easier acid denaturation of the double helix. The results, that are dose dependent, would point to both intercalation and cross-linking of DNA by 5,6-dihydroxyindole and its oxidation product(s). 3H-L-tyrosine deriving radioactivity, bound to nuclear DNA, is higher at low pH, (5.6) if compared to pH 6.8. The highest radioactivity bound to cell DNA is found during the transition from the amelanotic to the melanotic phenotype in human melanoma cell lines. As a control, the binding of 3H-L-tyrosine radioactivity to human prostate fibroblast DNA was investigated.
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PMID:Molecular approach to the nucleo-melanosomal interaction in human melanoma cells. 904 48

Despite the importance of the substrate 4-hydroxyanisole in melanoma therapy, the kinetics of its oxidation catalyzed by tyrosinase has never been properly characterized. This approach is reported here for the first time. The applicability to 4-hydroxyanisole of the reaction mechanism of tyrosinase previously proposed for other monophenols has been corroborated. The Michaelis constant for the oxidation of 4-hydroxyanisole catalyzed by mushroom tyrosinase was (62 +/- 1.5) microM at pH 7 and increased when the pH decreased, reaching a value of (195 +/- 5) microM at pH 5.5. However the maximum steady-state rate, whose value was (0.54 +/- 0.01) microM/min, did not change with the pH. The apparent catalytic constant was (184 +/- 5) s-1, around twenty three times higher than that previously described for L-tyrosine (8 s-1).
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PMID:Kinetic study of the oxidation of 4-hydroxyanisole catalyzed by tyrosinase. 916 22

Melanomas are highly clonogenic. Genetic variability and polymorphism of tumour cell populations have been reported. However, no direct evidence of mutator activity as a source of genetic polymorphism for melanoma cells has been described. Some intermediates of melanin synthesis are cytotoxic and genotoxic and their mutagenic power has been described. We show here that the rate of sister chromatid exchange (SCE) of the line of human melanoma cells used varies with the concentration of the melanin precursor L-tyrosine, in the culture medium. An increase of melanin synthesis results in increased SCE rates. The highest values of SCEs are found in melanotic melanoma cells compared with the amelanotic ones. Indeed we present evidence that melanoma cells show higher levels of SCE when compared with normal human lymphocytes, and to the SCE frequencies derived from the literature on the lymphocytes of familial malignant melanoma, sporadic malignant melanoma patients and the lymphocytes of relatives of familial and sporadic melanoma patients.
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PMID:Sister chromatid exchange (SCE) rates in human melanoma cells as an index of mutagenesis. 923 67

Detergent solubilized extracts of the cochleae of adult gerbils (Meriones unguiculatus) contain a tyrosine hydroxylase activity measurable by the radiometric method of Pomerantz. This activity is not related to Fenton-type reactions, since it is not inhibited by free radical scavengers and is heat and protease sensitive. It does not appear to be related to a peroxidase (EC 1.11.1.7) since it is neither dependent on H2O2, nor inhibited by catalase (EC 1.11.1.6). The involvement of a tyrosine hydroxylase (EC 1.14.16.2) related to catecholamine synthesis is also unlikely, since the activity is highly sensitive to 2-mercaptoethanol and is not increased by addition of tetrahydrobiopterin. The activity in crude inner ear extracts displayed an unusual maturation behaviour, with a slow activation upon aging at 4 degrees C. Fully active enzyme displayed Michaelis-Menten kinetics, with a Km for L-tyrosine of 47 microM. Cochlear tyrosine hydroxylase, but not melanoma tyrosinase (EC 1.14.18.1), was inhibited by o-phenanthroline, and was not dependent on L-DOPA as cofactor for full enzymatic activity. Crude extracts were also able to catalyze L-DOPA oxidation and melanin formation from either L-tyrosine or L-DOPA. The tyrosine hydroxylase, DOPA oxidase and melanin formation activities most probably resided in the same molecule, as suggested by inhibition studies. A tyrosine hydroxylase and melanin formation activity with identical properties was found in primary cultures of stria vascularis melanocytes. Immunochemical evidence confirmed the absence of either the tyrosinase encoded for by the albino locus, or the tyrosinase isoenzyme TRP1, encoded for by the brown locus. Conversely, an immunorreactive band of molecular weight 70 kDa was specifically recognized by a tyrosinase polyclonal antiserum in Western blot experiments. These results prove that melanogenesis in the cochlea, and likely in other extracutaneous locations such as the brain, is catalyzed by enzymatic systems different from, but related to tyrosinase.
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PMID:Melanin formation in the inner ear is catalyzed by a new tyrosine hydroxylase kinetically and structurally different from tyrosinase. 927 Dec 51

A first procedure was devised for determining 3,4-dihydroxyphenylalanine (L-DOPA) in human plasma by isocratic RP-HPLC coupled with electrochemical detection. A second procedure was devised for determining 3-hydroxyphenylalanine (L-tyrosine) in human plasma by isocratic RP-HPLC coupled with fluorescence detection. These methods were used to ascertain the L-DOPA/L-tyrosine ratio in plasma of patients with melanoma. Reference values were established by analysis of the L-DOPA/L-tyrosine ratio in the plasma of 35 normal healthy subjects. For 29 patients diagnosed as having melanoma without metastasis, the L-DOPA/L-tyrosine (11.96 x 10(-5) +/- 2.69 x 10(-5)) level was not significantly different from that of 35 normal controls (11.20 x 10(-5) +/- 2.92 x 10(-5)). However, this level was significantly increased (p < 0.05) in the plasma of 17 patients with developing metastasis (21.02 x 10(-5) +/- 4.68 x 10(-5)).
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PMID:Determination of the L-DOPA/L-tyrosine ratio in human plasma by high-performance liquid chromatography. Usefulness as a marker in metastatic malignant melanoma. 930 Sep 3


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