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

Abstract

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