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

J Photochem Photobiol B. 1998 Sep;45(2-3):131-5. doi: 10.1016/s1011-1344(98)00171-7.

Abstract

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.

MeSH terms

  • Aminolevulinic Acid / pharmacology*
  • Cell Line
  • Cell Line, Transformed
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Gene Expression / drug effects
  • Humans
  • Kinetics
  • Photosensitizing Agents / pharmacology*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • Proto-Oncogene Proteins c-myc / genetics*
  • Protoporphyrins / metabolism*

Substances

  • MAS1 protein, human
  • Photosensitizing Agents
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • Protoporphyrins
  • Aminolevulinic Acid
  • protoporphyrin IX