The Radiosensitivity of Human Neuroblastoma Cells Grown As Multicellular Tumour Spheroids

[摘要] Multicellular Tumour Spheroids (MTS) are a useful in vitro models of human cancer. Two cell lines - NB1-G and 1MR-32 - derived from two human neuroblastomas, were grown as MTS and were subjected to single, split and fractionated irradiation. The NB1-G MTS line is radiosensitive, with low capacity for repair of sublethal damage, which indicated that NB1-G may be a suitable cell line to test the theoretical advantage of hyperfractionation. The single dose response of 1MR-32 MTS, suggested that, intypically for neuroblastoma, 1MR-32 cells possessed a significant 'shoulder' on the cell survival curve. Fractionated radiation regimes were designed to be theoretically isoeffective for damage to late responding normal tissues (calculated using the linear-quadratic mathematical model with alpha/beta = 3GY). The radiation responses of MTS were evaluated using the end-points of regrowth delay and 'proportion cured' Regimens using smaller doses per fraction were found to be markedly more effective in causing damage to the NB1-G MTS, as assessed by either end-point. The isoeffective regimens caused approximately equal damage to 1MR-32 spheroids also. The findings were consistent with a substantial repair capacity for 1MR-32 MTS and implied that the well-known clinical heterogeneity of neuroblastoma might extend to its cellular radiobiology. These experimental findings support the proposal that hyperfractionation should be a therapeutically advantageous strategy in the treatment of tumours whose radiobiological properties are similar to those of the MTS neuroblastoma line NB1-G but not in the case of 1MR-32 MTS. On the basis of these results, it seems plausible that hyperfractionation would not be a universally advantageous strategy, but one whose efficacy is likely to depend on being able to select aporopriate tumours for this form of treatment.

[发布机构] University:University of Glasgow

[关键词] Cellular biology, Oncology