Pretreatment growth environments alter the sensitivity of tumor cells to cytotoxic agents

The effects of pretreatment growth conditions on the sensitivity of tumor cells to various cytotoxic agents were investigated using murine Ehrlich ascites tumor cells grown in two different environments. The tumor cells adapted to grow in the peritoneal cavity of mice were found to be more sensitive to ionizing radiation, oxygen toxicity, doxorubicin, and bleomycin than tumor cells adapted to grow in vitro. However, there was no difference in their sensitivity to 5-fluorouracil. One obvious difference between these two growth environments is oxygen tension; it is between 2.6 and 5.2% (20-40 mmHg) for the peritoneal cavity and 21% (159 mmHg) for the regular tissue culture. To investigate the role of oxygen tension, tumor cells from the peritoneal cavity were grown in tissue culture having either 21% O₂ or 4% O ₂ in the gas phase. Within 4 d, tumor cells that were exposed to 21% O₂, but not to 4% O₂, in vitro gradually became as resistant to cytotoxic agents as the tumor cells continuously cultured in vitro under 21% O₂. It appears that the adaptation of tumor cells to different environments having different partial pressure of oxygen alters their sensitivity not only to oxygen toxicity but also to other cytotoxic agents that damage or kill cells by generating free radicals.