Heat induction of reporter gene expression via the gadd153 promoter and its possible application to hyperthermia treatment of cancer

The use of the gadd153 promoter to induce expression of a reporter gene und er heat stress conditions was investigated, since the results of previous s tudies have suggested that the gadd153 promoter is likely to be activated b y the indirect effects of hyperthermia, that is, by DNA damage that occurs when reactive oxygen species are produced by heat stress. The optimum tempe rature for a significant induction was found to be between 41 and 43 degree s C and increased expression of the reporter gene was observed at about 24 h after the heat treatment. Under these conditions, the cell integrity was not altered morphologically and the growth stopped temporarily, while the v iability was maintained. A second increase in expression occurred at a late r stage when the cells were severely damaged at 43-45 degrees C. At these t emperatures, the cellular morphology showed significant alteration and the growth was strongly arrested. This is likely to be due to a different mecha nism which could involve DNA repair processes. It is expected that this met hod of induction can be exploited to drive the production of a protein of i nterest in a cancer treatment program that includes hyperthermia.