COLLATERAL RESISTANCE TO PHOTON AND NEUTRON-IRRADIATION IS ASSOCIATED WITH ACQUIRED CISPLATINUM RESISTANCE IN HUMAN OVARIAN TUMOR-CELLS

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 [4]. 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.