In-vitro study on ALA-induced endogenous protoporphyrin IX as photosensitizer for photodynamic tumor diagnosis and therapy

K. Ueberriegler; D. Fiedler; Thomas Verwanger; Gerlinde Schnitzhofer; E. Banieghbal; Barbara E. Krammer

doi:10.1117/12.316627

14 July 1998 In-vitro study on ALA-induced endogenous protoporphyrin IX as photosensitizer for photodynamic tumor diagnosis and therapy

K. Ueberriegler, D. Fiedler, Thomas Verwanger, Gerlinde Schnitzhofer, E. Banieghbal, Barbara E. Krammer

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Proceedings Volume 3423, Second GR-I International Conference on New Laser Technologies and Applications; (1998) https://doi.org/10.1117/12.316627
Event: Second GR-I International Conference on New Laser Technologies and Applications, 1997, Olympia, Greece

Abstract

Photodynamic tumor diagnosis and therapy is efficiently carried out by endogenous protoporphyrin IX as photosensitizer, induced by external addition of the precursor 5-aminolevulinic acid (ALA). In the present study, PpIX localization and photodynamically induced damage was investigated in normal and transformed human fibroblasts. PpIX formation reaches its maximum after incubation for at least 20 h with 700 (mu) g/m1 ALA, and increases with the pH- value. ALA has to be given 20-30 times more than external PpIX in order to produce the same cytotoxic damage. As detected by Low Light Imaging, PpIX is generated in the mitochondria, released to the cytoplasm and distributed to cytoplasma and nuclear membranes.The nucleus is not stained. Intracellular targets of PpIX damage after irradiation are mainly mitochondria, ER and nuclear membrane. The organelles show a decomposition pattern, which resembles apoptotic morphology and occurs faster in the co-cultivated transformed than in the normal cells. ALA-treated hepatocytes produce micronuclei and chromosomal aberrations, which indicates some mutagenic potential. Expression studies of the (proto)oncogenes c-myc and bcl-2 sublethally treated fibroblasts by quantitative RT-PCR show high deviations from the constitutive expression level, which are accompanied by cell cycle disturbances, indicating a possible precursor role to apoptosis introduction.

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K. Ueberriegler, D. Fiedler, Thomas Verwanger, Gerlinde Schnitzhofer, E. Banieghbal, and Barbara E. Krammer "In-vitro study on ALA-induced endogenous protoporphyrin IX as photosensitizer for photodynamic tumor diagnosis and therapy", Proc. SPIE 3423, Second GR-I International Conference on New Laser Technologies and Applications, (14 July 1998); https://doi.org/10.1117/12.316627

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KEYWORDS

Tumors

Luminescence

Photodynamic therapy

Cell death

In vitro testing

Skin

Cancer

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