Mechanisms of radiation resistance in cultured cells

James Russell
To investigate cellular radioresistance, three approaches were adopted. These were: to examine claims in the literature that growing cells as spheroids enhances their resistance to ionising radiation; to follow reports that cells transfected with ras oncogenes became more radioresistant; and to isolate a radioresistant subline from a radiosensitive human neuroblastoma cell line. It is known that for some cell lineages, culturing the cells as three-dimensional aggregates (spheroids), leads to an
more » ... increase in their radioresistance, relative to monolayers, and it has been proposed that this "contact effect" is related to the presence of inter-cellular gap junctional communication in the spheroid. This claim was investigated by testing two cell lines which were shown to form gap junctions. No contact effect could be demonstrated in either case. The existence of gap junctional communication is not sufficient to confer a contact effect, though the possibility remains that it is a necessary component. The prevalence of the contact effect in human tumour cell lines was examined by means of a literature survey. Of 27 lines for which published data was available, approximately one third showed a contact effect, and these lines were, on average, relatively radiosensitive, when grown as monolayers. However, an attempt to identify more instances of the contact effect by examining human neuroblastoma cell lines failed. (Neuroblastoma lines are known to be, in general, more than usually radiosensitive.) The effect of transfection with the oncogenes H-ras and c-myc was examined using a mink epithelial line, Mv1Lu. No alteration in radiosensitivity was observed in the transfected lines. These transfected lines were monoclonal in origin. There seemed to be little clonal variation in the parent line in terms of radiosensitivity. Five independent clones were established. Analysis of variance showed that in terms of radiosensitivity, they all belonged to the same population. This suggests that background variation in the radiosensitiv [...]
doi:10.5525/gla.thesis.71522 fatcat:jurf3mbqjzca3nk6h24ipnygku