|Budget Amount *help
¥3,900,000 (Direct Cost : ¥3,900,000)
Fiscal Year 2003 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 2002 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 2001 : ¥600,000 (Direct Cost : ¥600,000)
Fiscal Year 2000 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Boron Neutron Capture Therapy (BNCT) is the therapy which utilize the nuclear fission energy to destroy the cancer by irradiation of neutron to the cancer part, where ^<10>B is previously selectively accumulated. The fission reaction is that ^<10>B + n-^7Li + a. At present, p-Boronophenylalanine (p-BPA) is used to accumulate ^<10>B selectively into malignant melanoma. In melanoma melanin synthesis is accentuated, and in the melanin synthesis organism, DOPA, DHI, DHICA, which are melanin precursors, exist in large quantities. By our ^<11>B-NMR study of aqueous solutions, it has become apparent that p-BPA complexes with these melanin precersors, and when the complexes are oxidized p-BPA is decomposed into boric acid and tyrosine. We have considered that the complex formation and decomposition correspond to the ^<10>B accumulation and release mechanism respectively.
In this study, using hamster melanoma, cell organelles which contain melanin precursors were fractionated, and p-BPA was addi
ng to each fractions, and the interactions between p-BPA and melanin precursors were investigated. Two kinds of fractions were prepared, that is, the small granule fractions(SGF), which contain many coated vesicles (CV) where melanin precursors are abundant and the large granule fractions(LGF), which contain premelanosome and melanosome, in both premelanosome and melanosome melanin polymers are abundant. Into the both fractions p-BPA was added and ^<11>B-NMR were measured. In SGF-p-BPA system, two hours after the mixing, a signal was appeared. The signal seems to be due to the p-BPA-melanin precursors complex. The signal increased with time and 8 hours after the mixing, the signal became a broad signal. In LGF p-BPA system, such signal was not observed.
Into the melanoma bearing hamsters p-BPA-fructose complex was administrated. At 2 and 10 hours after administrations, melanoma of hamsters were fractionated, and ^<11>B-NMR was measured. The peak of p-BPA-melanin precursors was not observed in any samples, but the peak of boric acid was observed in all samples.
By ^<11>B-NMR measurements, the following results were obtained. Melanin is divided into two types, i. e., pheomelanin and eumelanin. p-BPA inhibits both melanin formations. p-BPA more complexes with monosaccharides than m-BPA. p-BPA complexes with dopamine. Less