Selective uptake of para-boronophenylalanine increases in amelanotic melanoma cells transfected by the tyrosinase gene.
To investigate the mechanism of uptake of para-boronophenylalanine (p-BPA), a capture agent for boron neutron capture therapy (BNCT) of melanoma and brain tumour, into melanoma cells, we studied the relationship between melanin synthesis and the concentration of boron using tyrosinase-deficient mouse amelanotic melanoma cells (A1059) and melanotic melanoma cells (TA1059). A1059 was established from mouse B16F10 cells, and TA1059 was constructed by transfecting human tyrosinase cDNA into A1059. The melanin content of TA1059 was 1.5-fold higher than that of B16F10, and was undetectable in A1059. The order of p-BPA uptake was TA1059 > B16F10 > A1059 at the time points examined, and the boron content of TA1059 was approximately 1.5-fold higher than that of B16F10. Our experimental findings indicated that melanin synthesis is a very important factor for characterizing the increase in accumulation of p-BPA in melanoma cells. A significant difference in boron uptake into TA1059 was observed between p-BPA and meta-BPA (m-BPA), but there were no apparent differences in the case of A1059. The difference in accumulation of p-BPA and m-BPA could be due to differences in the properties of p-BPA as a tyrosine analogue needed for melanin synthesis.
Hiratsuka
J
J
Department of Radiation Oncology, Kawasaki Medical School, Kurashiki, Japan. hiratuka@med.kawasaki-m.ac.jp
Kondoh
H
H
Tsuboi
T
T
Yoshino
K
K
Imajo
Y
Y
Mishima
Y
Y
D000818:Animals; D001896:Boron Compounds / Q000493:pharmacokinetics*; D015870:Gene Expression; D006801:Humans; D008543:Melanins / Q000096:biosynthesis; D018328:Melanoma, Amelanotic / Q000235:genetics* / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D014442:Monophenol Monooxygenase / Q000172:deficiency / Q000235:genetics*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D011838:Radiation-Sensitizing Agents / Q000493:pharmacokinetics*; D014162:Transfection; D014407:Tumor Cells, Cultured
D001896:Boron Compounds; D008543:Melanins; D011838:Radiation-Sensitizing Agents; D010649:Phenylalanine; D014442:Monophenol Monooxygenase; C033685:4-boronophenylalanine