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 induction, photodynamic tumour therapy also shows a moderate mutagenicity. The oncogenes responsible for it can be distinguished from their proto-oncogenic precursors by an irreversible increase in their constitutive expression. Transient changes of the expression level of (proto) oncogenes can indicate the beginning of disturbances in the cell homeostasis: many of these genes have a normal function in proliferation or play a role in apoptosis. In this study, therefore, quantitative determination of the expression of the (proto) oncogenes c-myc and bcl-2 in normal and transformed human fibroblasts at different times following photodynamic treatment with 5-aminolaevulinic acid-stimulated endogenous protoporphyrin IX and low-dose irradiation has been carried out by quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The aim is to investigate if irreversibly increased (proto) oncogene expression can be found, and if expression changes are involved in cell-cycle alterations (detected in a parallel study) and in initiation of apoptotic 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 cell 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 normal fibroblasts.
Verwanger
T
T
Institute of Physics and Biophysics, University of Salzburg, Austria.
Schnitzhofer
G
G
Krammer
B
B
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D002460:Cell Line; D002461:Cell Line, Transformed; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D017319:Photosensitizing Agents / Q000494:pharmacology*; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D011524:Protoporphyrins / Q000378:metabolism*
C000715470:MAS1 protein, human; D017319:Photosensitizing Agents; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX