Britten R A, Warenius H M, White R, Browning P G, Green J A
CRC Department Radiation Oncology, University of Liverpool, Clatterbridge Hospital, Bebington, Wirral, U.K.
Radiother Oncol. 1990 Aug;18(4):357-63. doi: 10.1016/0167-8140(90)90116-e.
High linear energy transfer (LET) fast neutrons for the local control of advanced head and neck tumours are currently being evaluated at several centres. Fast neutrons are believed to produce more direct, and less OH mediated damage than photons, and consequently be less affected by intracellular thiol levels. Chemoresistant tumours with elevated thiol levels may therefore be more effectively controlled by fast neutron therapy than by photons. The "in vitro" radiation response of melphalan sensitive and resistant human ovarian tumour cell lines has demonstrated that melphalan resistance confers a 1.5-fold level of cross-resistance to photons, primarily attributable to a 2-fold decrease in the alpha component in the resistant OAW42/MER cell line. Pretreatment of the melphalan-resistant line with the thiol depleting agent buthionine sulphoximine (BSO) restored the magnitude of alpha to a value similar to that in the chemosensitive cell line. The survival curves of these cell lines following neutron irradiation were near exponential, with similar values of alpha. This study has demonstrated that melphalan resistant tumour cells are cross-resistant to photon irradiation, but not to fast neutrons. The mechanism of cross-resistance has yet to be determined, but glutathione (GSH) appears to be involved.
目前，多个中心正在评估高传能线密度（LET）快中子对晚期头颈肿瘤的局部控制效果。与光子相比，快中子被认为能产生更直接、且由羟基自由基介导的损伤更少，因此受细胞内硫醇水平的影响较小。硫醇水平升高的化疗耐药肿瘤，可能通过快中子治疗比光子治疗得到更有效的控制。美法仑敏感和耐药的人卵巢肿瘤细胞系的“体外”辐射反应表明，美法仑耐药赋予了对光子1.5倍水平的交叉耐药性，这主要归因于耐药的OAW42/MER细胞系中α组分降低了2倍。用硫醇消耗剂丁硫氨酸亚砜胺（BSO）预处理美法仑耐药细胞系，可使α的大小恢复到与化疗敏感细胞系相似的值。这些细胞系在中子照射后的存活曲线接近指数曲线，α值相似。这项研究表明，美法仑耐药肿瘤细胞对光子照射有交叉耐药性，但对快中子没有。交叉耐药的机制尚未确定，但谷胱甘肽（GSH）似乎参与其中。
