Expression kinetics of the (proto)oncogenes c-myc and bcl-2 following photodynamic treatment of normal and transformed human fibroblasts with 5-aminolaevulinic acid-stimulated endogenous protoporphyrin IX

In the same way as common tumour therapies can cause secondary tumour induc tion, photodynamic tumour therapy also shows a moderate mutagenicity. The o ncogenes responsible for it can be distinguished from their proto-oncogenic precursors by an irreversible increase in their constitutive expression. T ransient changes of the expression level of (proto)oncogenes can indicate t he beginning of disturbances in the cell homeostasis: many of these genes h ave a normal function in proliferation or play a role in apoptosis. In this study, therefore, quantitative determination of the expression of the (pro to)oncogenes c-myc and bcl-2 in normal and transformed human fibroblasts at different times following photodynamic treatment with 5-aminolaevulinic ac id-stimulated endogenous protoporphyrin IX and low-dose irradiation has bee n carried out by quantitative reverse transcriptase polymerase chain reacti on (RT-PCR). The aim is to investigate if irreversibly increased (proto)onc ogene expression can be found, and if expression changes are involved in ce ll-cycle alterations (detected in a parallel study) and in initiation of ap optotic processes. The results show: (1) no mutagenic risk, since the over- expression of c-myc and bcl-2 is transient; (2) an interaction of bcl-2 and c-myc associated with an increase of the proliferative activity of the cel l cycle of transformed cells; (3) a possible role of bcl-2 in counteracting processes that could be at least precursors for apoptosis induction; and ( 4) higher constitutive expression of both genes in transformed than in norm al fibroblasts. (C) 1998 Elsevier Science S.A. AU rights reserved.