Inhibition of L-tyrosine-induced micronuclei production by phenylthiourea in human melanoma cells.
It was previously found that L-tyrosine oxidation product(s) are cytotoxic, genotoxic and increase the sister chromatid exchange (SCE) levels in human melanoma cells. In this work, the micronucleus assay has been performed on human melanotic and amelanotic melanoma cell lines (Carl-1 MEL and AMEL) in the presence of 1.0, 0.5 and 0.1 mM L-tyrosine concentrations to investigate if melanin synthesis intermediate(s) increase micronuclei production. L-Tyrosine oxidation product(s) increased the frequency of micronuclei in melanoma cells; 0.1 mM phenylthiourea (PTU), an inhibitor of L-tyrosine oxidation by tyrosinase, lowered the micronucleus production to the control levels. The culture of melanoma cells with high L-tyrosine in the culture medium resulted in a positive response to an ELISA-based apoptotic test. For comparison the effect of L-tyrosine on micronuclei production in human amelanotic melanoma cells was also investigated; the micronucleus production in the presence of 1 mM L-tyrosine in the culture medium was lower than that found with melanotic melanoma cells of the same cell line. The data suggest that melanin synthesis intermediates arising from L-tyrosine oxidation may cause micronuclei production in Carl-1 human melanoma cells; the addition of PTU in the presence of L-tyrosine decreased the frequency of micronuclei to about the control values thus the inhibition of melanogenesis may have some clinical implication in melanotic melanoma.
Poma
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Department of Basic and Applied Biology, Faculty of Sciences, University of L'Aquila, Italy. cellular@univaq.it
Bianchini
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Miranda
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D017209:Apoptosis / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000235:genetics*; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics*; D018328:Melanoma, Amelanotic / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D015162:Micronucleus Tests; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010670:Phenylthiourea / Q000494:pharmacology*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D003571:Cytochalasin B; D014443:Tyrosine; D010670:Phenylthiourea; D014442:Monophenol Monooxygenase