Ribonucleotide reductase in melanoma tissue |
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Authors: | G Lassmann B Liermann W Arnold K Schwabe |
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Institution: | (1) Central Institute of Molecular Biology, Roessle-Strasse 10, O-1115 Berlin-Buch, Federal Republic of Germany;(2) Central Institute of Cancer Research, Roessle-Strasse 10, O-1115 Berlin-Buch, Federal Republic of Germany |
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Abstract: | Summary The characteristic EPR doublet of tyrosine radicals of the growth-regulating enzyme ribonucleotide reductase was detected in human melanoma tissue grown in nude mice. This was possible through the use of an amelanotic melanoma that does not exhibit disturbing EPR signals from melanin. The content of tyrosine radicals is higher in young tumor tissues than in older ones. The clinically applied antimelanotic drug, 4-hydroxyanisole, inhibits ribonucleotide reductase in Ehrlich ascites tumor cells as demonstrated by a pronounced quenching of tyrosine radicals (IC50=5 M). In amelanotic melanoma tissue tyrosine radicals of the enzyme are also quenched by 4-hydroxyanisole in concentrations down to 50 M. Thus, the inactivation of ribonucleotide reductase, which provides deoxyribonucleotides for DNA synthesis, may be a hitherto unexpected mechanism for the antitumor action of 4-hydroxyanisole.Abbreviations EPR
electron paramagnetic resonance
- RR
ribonucleotide reductase
- 4-HA
4-hydroxyanisole |
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Keywords: | Ribonucleotide reductase Melanoma EPR Tyrosine radical 4-Hydroxyanisole |
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