CROSS-SENSITIVITY TO X-RADIATION AND TYPE-I AND TYPE-II DNA TOPOISOMERASE INHIBITORS IN A RANGE OF HUMAN AND RODENT CELL-LINES

We compared the relative X-radiation response of confluent (i.e. essen tially non-proliferating) cultures of three human tumor (U-87MG, Mel-3 , HT-144), one human normal (AG1522) and two rodent normal (AA8, V3) c ell lines to their relative sensitivities to a DNA topoisomerase (topo ) II poison (etoposide) and to a topo I poison (camptothecin). The rel ative sensitivity of these cell lines to etoposide (for 8 h exposure a t 37 degrees C) is extremely similar to their relative X-radiation sen sitivity, suggesting a direct correlation between X-radiation sensitiv ity and susceptibility to killing by topo II poison. The relative sens itivities of these cell lines to camptothecin (also 8 h, 37 degrees C exposure) also agree generally with their relative X-radiation sensiti vities although the correlation is not as good as for etoposide. In ad dition, exponential phase (i.e, actively proliferating) cultures of th e radiosensitive HT-144 cells are more susceptible to killing by both etoposide and camptothecin than the radioresistant Mel-3, confirming p reviously reported cross-sensitivities between X-radiation and topo po isons in actively proliferating cultures of other types of cell lines. Hence our results suggest that the previously reported cross-sensitiv ity between topo II poisons and X-radiation in actively proliferating rodent cell lines is also observed in 'non-proliferating' rodent and h uman cell lines. Additionally, there is cross-sensitivity between topo I poisons and X-radiation in both rodent and human cell lines as well .