Enhanced lethal effect of thermal neutron radiation on melanoma cells by increased accumulation of ^<10>B-compound within target cells

热中子俘获治疗(TNCT)是一种很有前途的选择性靶向肿瘤细胞照射的方法。目的：寻找一种新的条件，使^&lt；10；B_1-对苯丙氨酸(^&lt；10&gt；B_1-bpa)在体外和体内比以前的条件更有效地掺入黑色素瘤细胞和体内，从而产生更有效的杀伤作用。结果与评论：(1)10&gt；B^1-BPA对黑色素瘤细胞的灭活作用呈剂量依赖关系，最高达80 g/ml。(2)Lineweaver-Burke图显示B_1-BPA对培养的B-16黑色素瘤细胞摄取~3H-酪氨酸有抑制作用。(3)含酪氨酸和苯丙氨酸缺陷型MEM(10-50；microrn&gt；G/ML)与含有酪氨酸和苯丙氨酸缺陷型MEM(10-50&lt；10&gt；B_2-BPA)预孵育的黑色素瘤细胞相比，TNCT的杀伤作用增强。(4)含10&lt；microrn&gt；10&gt；B_1-BPA/ml的D-MEM孵育的B-16黑色素瘤细胞的B含量比普通MEM高4倍。(5)用不含酪氨酸和苯丙氨酸的饲料喂养7天的仓鼠移植的Greene黑色素瘤比常规饲料喂养的仓鼠高1.2~2.4倍。这些来自体内和体内实验的结果强烈表明，即使在热中子照射的人类黑色素瘤中，不含酪氨酸和苯丙氨酸的饮食也可以使黑色素瘤组织失活。

Thermal neutron capture therapy (TNCT) represents a promising modality for selective targetting irradiatin of tumor cells. The crucial point of successful use of TNCT for melanoma is how the ^<10>B-compound is selectively incorporated into melanoma cells and accumulate in melanoma tissue after administrations of the chemicals.Aim: To find a new condition in which ^<10>B_1-paraboronophenylalanine (^<10>B_1-BPA) is incorporated more effectively into melanoma cells in vitro and also invivo than the previous conditions, resulting in a more efficient lethal effect of ^<10>B_1-BPA-TNCT on melanoma cells and melanoma.Results and Comments: (1)Inactivation of melanoma cells by TNCT increased in dose dependent manner of ^<10>B^1-BPA upto 80 <micrn>g/ml. (2)Inhibitory effect of ^<10>B_1-BPA on the uptake of ^3H-tyrosine using cultured B-16 melanoma cells was shown by Lineweaver-Burke plot. (3)Enhanced lethal effect of TNCT was obtained when melanoma cells were pre incubated with tyrosine and phenylalanine deficient MEM (D-MEM) containg ^<10>B_1-BPA(10-50<micrn>G/ML) compared to that of melanoma cells preincubated with the usual MEM containg the same account of ^<10>B_2-BPA. (4)^<10>B content of B-16 melanoma cells incubated with D-MEM containg 10<micrn>g ^<10>B_1-BPA/ml was 4 times higher than that of usual MEM. (5)Greene's melanoma transplanted in hamster that had been fed with tyrosine and phenylalanie-free diet for 7 days before administartion incorporated 1.2-2.4 times higher ^<10>B than that of hamster that had been fed with usual diet. These results obtained from in vivtro and in vivo experiments strongly subject that tyrosine- and phenylalanine-free diet could inactivate melanoma tissue even in human melanoma irradiated with thermal neutron.