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. 1991 Mar;117(2):91–95. doi: 10.1007/BF01613130

Ribonucleotide reductase in melanoma tissue

EPR detection in human amelanotic melanoma and quenching of the tyrosine radical by 4-hydroxyanisole

G Lassmann 1,✉, B Liermann 1, W Arnold 2, K Schwabe 2
PMCID: PMC12201543  PMID: 1848862

Abstract

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 μM). In amelanotic melanoma tissue tyrosine radicals of the enzyme are also quenched by 4-hydroxyanisole in concentrations down to 50 μM. 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.

Key words: Ribonucleotide reductase, Melanoma, EPR, Tyrosine radical, 4-Hydroxyanisole

Abbreviations

EPR

electron paramagnetic resonance

RR

ribonucleotide reductase

4-HA

4-hydroxyanisole

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