INFLUENCE OF AN AUTOCRINE MULTITHERAPY RESISTANCE FACTOR ON RADIATIONRESPONSES OF MELANOMA-CELLS

An autocrine multitherapy resistance factor (MTRF) produced by a radio resistant subclone of S91 mouse melanoma (S91/l3) causes an increase i n radioresistance of a radiosensitive subclone (S91/amel). MTRF has no effect on the survival of S91/l3, which is already relatively resista nt to gamma-irradiation. In this study, we examined the effect of MTRF in the form of S91/I3 conditioned medium or as S91/I3 heavily-irradia ted cells (I3-HRCells) on cellular responses of S91/amel cells after e xposure to gamma-rays . Target S91/amel cells retained more than half of their ability to respond to rescue by MTRF on day 4 after exposure to 3 Gy. Continuous presence of MTRF during colony formation was neces sary for maximum plating efficiency. Although the extent of double str and DNA breakage and repair was the same in Sg1/amel and S91/I3, split -dose recovery experiments with MTRF revealed previously undetected re pair of sublethal damage in S91/amel cells. MTRF did not alter the ext ent of potentially lethal damage repair (PLDR) in S91/I3 or S91/amel. S91/amel cells were more responsive to MTRF if they had been harvested from confluent dishes, while S91/I3 cells produced a more effective f actor if they had been harvested in exponential phase. These findings demonstrate that MTRF has unique properties. It does not appear to be involved in genome repair since it does not alter the extent of PLDR a nd it is effective when added to cells after complete split-dose recov ery has occurred.