Radiosensitivity of tumors and derived cells in culture

In man, various types of tumors, e.g. some lymphomas, can be eradicated by a total dose of 3000 to 4000 rad of X-rays, applied at 200 rad per fraction in 3 to 4 wk. Other types of tumors, e.g. well differentiated adenocarcinomas, show little if any macroscopically observable response to treatments with a total dose of 7000 rad of X-rays applied in 6 to 7 wk. Many characteristics and factors have been suggested to be responsible for these differences, e.g., repair of sub-lethal and potentially lethal damage, cell proliferation kinetics, hypoxic conditions of cells in necrotic tumors, intercellular contacts causing increased repair of damage, tumor embedding in different normal tissues and immunologic defenses of the host. In addition to these factors it has been recognized that differences may exist in intrinsic cellular radiosensitivity of tumors possibly related to their tissue of origin. The importance of these intrinsic cellular differences relative to the other factors has not been adequately evaluated, however, although they might be very significant with respect to the interpretation of variation among radiation responses of tumors. Consideration of the results obtained with 10 tumorigenic cell lines, indicates that the doses required to yield 50% reproductive death are largest for cells derived from the carcinomas, while the most sensitive cells are those derived from a lymphosarcoma and from a lymphocytic leukemia, while cells from mesenchymal sarcomas show an intermediate sensitivity. However, if cells from more tumor types are investigated, it is likely that the distributions of sensitivities will show overlapping regions, i.e. it cannot be concluded that cells from all carcinomas are significantly more resistant than cells from all sarcomas. The differences in radiosensitivity observed in vitro between tumorigenic cell lines are likely to have a significant influence on the response of tumors which can be grown by inoculation of these cells in syngeneic animals. Studies of tumor growth delay after single doses between 1000 and 5000 rad of X-rays have shown that e.g. the ureter squamous cell carcinoma RUC-2 is very resistant. However, studies with fractionated small doses are required to further elucidate the importance of various other factors and characteristics. On the basis of presently available data it can be predicted, that the influence of differences in intrinsic cellular radiosensitivity is at least of equal importance in determining tumor responses to fractionated treatments, as the influence of hypoxic cells or of cell kinetics. With respect to improvement of radiotherapy of cancer, investigations directed at an analysis of causes of intrinsic sensitivity differences among cells from different tumors, might yield important results.