Photodynamically induced cell cycle and gene expression changes: Precursors of apoptosis introduction?

Photodynamic tumor therapy is able to induce apoptosis with many photosensitizers. Apoptosis is based on changes in gene expression and correlated to cell cycle activities. In this study, therefore, quantitative determination of the expression of the (proto)oncoges c-myc and bcl-2 in normal and transformed fibroblasts following PDT with ALA and low dose irradiation was connected with cell cycle analysis in order to investigate, if a risk for occurrence of secondary tumors by irreversibly increased oncogene expression can be found, if phases of the cell cycle show selective sensitivity to the therapy, and if changes in one of the two or both parameters may either precede or prepare an introduction of apoptosis. The results show 1) no mutagenic risk by timely limited overexpression of c-myc and bcl-2, 2) no selective cell cycle sensitivity to the therapy; but, in contrary, sustained increase of the proliferative activity of the transformed cells by the interaction of bcl-2 and c-myc, indicating a risk of promotion of tumor regrowth in sublethally damaged areas, 3) the introduction of apoptotic processes by low dose PDT in the cytoplasm/mitochondria and less in the nucleus. Transformed cells show higher constitutive gene expression and proliferative activities than normal cells.