Abstract
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.
We’re sorry, something doesn't seem to be working properly.
Please try refreshing the page. If that doesn't work, please contact support so we can address the problem.
References
Glatzer L, Dora A, Rincon, Eisenstark A: The binding of near-ultraviolet light-induced tryptophan photoproduct(s) to DNA. Biochim Biophys Acta 418: 137–145, 1976
Eisenstark A: Genetic recombination in bacteria. Ann Rev Gen 11: 369–396, 1977
Miranda M, Bonfigli A, Zarivi O, Manilla A, Cimini AM, Arcadi A: Restriction patterns of model DNA treated with 5,6-dihydroxyindole, a potent cytotoxic intermediate of melanin synthesis: effect of u.v. irradiation. Mutagenesis 2(1): 45–50, 1987
Miranda M, Amicarelli F, Bonfigli A, Poma A, Zarivi O, Arcadi A: Mutagenicity test for unstable compounds, such as 5,6-dihydroxyindole, using an Escherichia coliHB101/ pBR322 transfection system. Mutagenesis 5: 251–255, 1990
Miranda M, Amicarelli F, Poma A, Ragnelli AM, Scirri C, Aimola PP, Masciocco L, Bonfigli A, Zarivi O: Cyto-genotoxic species leakage within human melanoma melanosomes. Molecular-Morphological correlations. Biochem Mol Biol Int 32(5): 913–922, 1994
Mishima Y: Macromolecular changes in pigmentary disorders. Arch Derm 91: 519, 1965
Miranda M, Botti D, Di Cola M: Possible genotoxicity of melanin synthesis intermediates: Tyrosinase reaction products interact with DNA in vitro. Mol Gen Genet 193: 395–399, 1984
Champoux JJ: Proteins that affect DNA conformation. Ann Rev Biochem 47: 449–479, 1978
Gellert M: DNA Topoisomerases. Ann Rev Biochem 50: 879–910, 1981
Wang JC: DNA Topoisomerases. Ann Rev Biochem 54: 665–697, 1985
Miranda M, Botti D, Bonfigli A, Arcadi A: 5,6-dihydroxyindole oxidation by mammalian, mushroom and amphibian tyrosinase preparations. Biochim Biophys Acta 841: 159–165, 1985
Wang JC, Kirkegaard K: In: Chirikjian JG, Papas TS (eds) Gene Amplification and Analysis, Vol 2. Elsevier, New York, 1981, pp 456–473
Miranda M, Amicarelli F, Poma A, Ragnelli AM, Arcadi A: Liposome entrapped tyrosinase: a tool to investigate the regulation of the Raper-Mason pathway. Biochim Biophys Acta 966: 276–286, 1988
Blin N, Stafford DW: Isolation of high molecular weight DNA. Nucleic Acids Res 3: 2303, 1976
Old JM, Higgs DR. In: Weatherall DJ (ed) Methods in Haematology, Vol 6. Churchill Livingstone, Edinburgh, 1983, pp 74–102
Hassan M, Fridovich I: Superoxide dismutases: detoxication of a free radical. In: Jakoby WB (ed) Enzymatic Basis of Detoxication, Vol 1. Academic Press, Inc., New York, 1980, pp 311–332
Miranda M, Urbani G, Di Vito L, Botti D: Inhibition of tyrosinase by indole compounds and reaction products. Protection by albumin. Biochim Biophys Acta 585: 398–404, 1979
Tomita Y, Harin A, Miruno C, Seiji M: Inactivation of tyrosinase by DOPA. J Invest Dermatol 75(5): 379–382, 1980
Chase JW, Williams KR: Single-stranded DNA binding proteins for DNA replication. Ann Rev Biochem 55: 103–136, 1986
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Miranda, M., Zarivi, O., Amicarelli, F. et al. Molecular approach to the nucleo-melanosomal interaction in human melanoma cells. J Neurooncol 31, 185–193 (1997). https://doi.org/10.1023/A:1005730724500
Issue Date:
DOI: https://doi.org/10.1023/A:1005730724500