Influence of an autocrine diffusible resistance factor on cell survival after exposure to therapeutic agents.

A subclone of Cloudman mouse melanoma cells (S91/I3) produces a resistance factor (RF) that increases the survival of a different but related subclone, S91/Amel, after exposure to either ultraviolet C (UVC) radiation or to mitomycin C (MMC). The presence of RF was deduced from experiments in which heavily irradiated S91/I3 cells were plated with the target S91/Amel cells. The effect of RF was also present in cell-free conditioned tissue culture medium (CM) from S91/I3 cultures. These results extend previous findings that both subclones produce an autocrine resistance factor (RF) that alters the radiation response of target S91/Amel cells making them less sensitive to death by low linear energy transfer (LET) ionizing radiation. S91/I3 cells are radioresistant relative to S91/Amel and produce the RF more effectively than S91/Amel. S91/I3 cells do not respond to the RF, being themselves, presumably, maximally stimulated. The significant findings are (1) the RF is effective at decreasing the killing of the target cells using cytotoxic agents that operate by different mechanisms; (2) The relative sensitivities of S91/Amel and S91/I3 to the toxic agents is not a factor in the responses of these cells to the RF: S91/Amel survivals are increased by the RF, those of S91/I3 are not; (3) the RF is elaborated by the melanoma cells whether or not they have been irradiated; it is, apparently, a normal cell product; (4) the RF is effective when added after the cytotoxic insult; its presence is not required during irradiation or drug treatment. The RF appears to act by novel mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)