In vitro prediction of inherent cellular radiosensitivity

Abstract

The principal objective in irradiating tumours is to permanently inhibit their reproductive ability. More than half of all malignancies are primarily treated with radiation but tumours of different histologies differ greatly in response to radiotherapy as well as individual patients displaying great variability in response to treatment. The need for reliable assays predicting tumour and normal tissue response to radiation is therefore a prime objective of clinical oncology. The requirement of such a test would be that it would relate to clinical outcome Le. the possibility of recurrence of disease or of tumour control as well as indicating whether the treatment should be administered more aggressively or not. These are important factors that, if known, could be used as part of the treatment planning in radiotherapy and selection of best therapy modality. The colony forming c1onogenic assay has been shown to be a reliable reflection of a cells ability to maintain reproductive integrity after radiation exposure. In this study it has successfully been used to demonstrate the surviving fraction of cells but has the limitation of cells needing to process the ability to form colonies. Cells from primary tumours do not readily form colonies and may display poor anchorage making this assessment of radiosensitivity in the clinic less desirable. These data are presented together with unpublished data obtained using the micronucleus assay. Micronuclei frequency (MNF) varies in different cell types with test doses and provides a means to rank the cell in terms of response to radiation. In normal cells a linear inverse correlation exits between MNF and cell survival. However, MNF does not rank malignant cells according to their intrinsic survival to radiation displaying a weak correlation between MNF and cell survival.