Britten R A, Peacock J, Warenius H M
CRC Oncology Research Unit, Department of Medicine, University of Liverpool, U.K.
Radiother Oncol. 1992 Mar;23(3):170-5. doi: 10.1016/0167-8140(92)90327-q.
The melphalan resistant variant of the human ovarian OAW42 tumour cell line has previously been shown to be collaterally resistant to photon irradiation, but not to fast neutrons. In the present study, the "in vitro" photon and neutron radiosensitivity of human ovarian OAW42 tumour cells with acquired resistance to cis-platinum has been studied, to determine whether a similar pattern of cross-resistance exists between cis-platinum and these ionising radiations. Analysis of SF2 values suggests that resistance to cis-platinum conferred a 3-fold decrease in sensitivity to photons, primarily attributable to a 5-fold decrease in the magnitude of the initial slope (alpha). Depletion of GSH by BSO restored the magnitude of alpha to a value similar to that of the parental line. However, cis-platinum resistant OAW42/CP cells, in contrast to melphalan resistant cells, were 1.5-fold more resistant to "fast" neutrons (assessed at D0.1 survival level) than the parental OAW42 cell line. The mechanism for the collateral resistance between cis-platinum, and both photons and neutrons remains to be determined, but although GSH levels may be directly, or indirectly involved in the collateral resistance to photons, they would appear not to involved with the mechanisms responsible for collateral neutron resistance, in the cis-platinum resistant human ovarian cell lines used in this study.
人类卵巢OAW42肿瘤细胞系的美法仑耐药变体先前已被证明对光子辐射具有交叉耐药性，但对快中子没有交叉耐药性。在本研究中，对获得顺铂耐药性的人类卵巢OAW42肿瘤细胞的“体外”光子和中子放射敏感性进行了研究，以确定顺铂与这些电离辐射之间是否存在类似的交叉耐药模式。对SF2值的分析表明，对顺铂的耐药性使对光子的敏感性降低了3倍，这主要归因于初始斜率（α）的大小降低了5倍。用丁硫氨酸亚砜胺耗尽谷胱甘肽（GSH）可使α的大小恢复到与亲本细胞系相似的值。然而，与美法仑耐药细胞相比，顺铂耐药的OAW42/CP细胞对“快”中子的耐药性（在D0.1存活水平评估）比亲本OAW42细胞系高1.5倍。顺铂与光子和中子之间交叉耐药的机制仍有待确定，但尽管GSH水平可能直接或间接参与对光子的交叉耐药，但在本研究中使用的顺铂耐药人类卵巢细胞系中，它们似乎与负责交叉中子耐药的机制无关。
