title: Phototoxicity of exogenous protoporphyrin IX and delta-aminolevulinic acid in the photo hen's egg test.
abstract: BACKGROUND
  Oxygen, appropriate light sources, and special photosensitizers are necessary to induce photochemical damage in tumor cells via photodynamic therapy (PDT) delta-aminolevulinic acid (ALA) is increasingly used in PDT, because topical or systemic administration of ALA induces accumulation of endogenous porphyrins preferentially in neoplastic tissues. Subsequent radiation with light of approximately 630 nm leads to selective damage of tumor cells. PDT should optimally leave peritumoral tissues unaffected, but only few data are reported on the effects and the time course of ALA-induced porphyrins in tumor-free tissues.
  
  
  METHODS
  Therefore, we studied the phototoxic effects of protoporphyrin IX (PP) and ALA-induced porphyrins in a recently established phototoxic model based on tumor-free tissue, the photo hen's egg test (PHET).
  
  
  RESULTS
  Employing this test procedure, PP provoked strong phototoxic reactions when irradiated with Ultraviolet A immediately and up to 30 h after substance application. In contrast, ALA induced a significant phototoxic effect only if irradiated 24 h after application.
  
  
  CONCLUSIONS
  Thus, we observed a delayed phototoxic effect of ALA in tumor-free tissue of the yolk sac (YS) blood vessel system. This delayed phototoxic response 24 h after ALA application is probably caused by endogenously synthesized porphyrins. In contrast, epithelial tumors show a maximum porphyrin accumulation 4-8 h after ALA application whereas in healthy human skin porphyrin synthesis is less intensive but prolonged with maximum levels 24-48 h after ALA application. Thus, ALA induced virtually the same delayed phototoxic effect in the tumor-free YS blood vessel tissue as in healthy human skin. These results show that the PHET is a useful model for the predictive preclinical risk assessment of exogenous or endogenous photosensitizers.
authors.affiliation: Department of Dermatology, Heinrich-Heine-University Duesseldorf, Moorenstrasse 5, D-40225 Duesseldorf, Germany. neumannt@uni-duesseldorf.de
authors.forename: Norbert J
authors.initials: NJ
authors.lastname: Neumann
authors.forename: Sandra
authors.initials: S
authors.lastname: Hanneken
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruzicka
authors.forename: Percy
authors.initials: P
authors.lastname: Lehmann
mesh_terms: D000622:Aminolevulinic Acid / Q000008:administration & dosage / Q000009:adverse effects*; D000818:Animals; D002642:Chick Embryo; D017484:Dermatitis, Phototoxic / Q000209:etiology*; D004195:Disease Models, Animal; D005544:Forecasting; D006470:Hemorrhage / Q000209:etiology; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000009:adverse effects*; D011524:Protoporphyrins / Q000008:administration & dosage / Q000009:adverse effects*; D011829:Radiation Dosage; D018570:Risk Assessment; D015996:Survival Rate; D013997:Time Factors; D014466:Ultraviolet Rays; D015017:Yolk Sac / Q000098:blood supply / Q000187:drug effects
chemical_list: D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX