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

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

• Authors: G Lassmanm, B Liermann, W Arnold, K Schwabe
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 117 Issue 2 Pg. 91-5 ( 1991) ISSN: 0171-5216 [Print] Germany
• PMID: 1848862 (Publication Type: Journal Article)

Chemical References

• Anisoles
• Free Radicals
• Tyrosine
• mequinol
• Ribonucleotide Reductases

Topics

• Animals
• Anisoles (pharmacology)
• Carcinoma, Ehrlich Tumor (drug therapy)
• Cell Division (drug effects)
• Electron Spin Resonance Spectroscopy
• Free Radicals
• Melanoma (drug therapy, enzymology)
• Mice
• Mice, Inbred ICR
• Ribonucleotide Reductases (biosynthesis)
• Tyrosine (metabolism)