Lack of effect of hyperoxia on photodynamic therapy and lipid peroxidation in three different cancer cell lines.
BACKGROUND
The use of photodynamic therapy (PDT) to treat malignant tumors involves a photosensitizing drug, light, and oxygen. Since PDT requires oxygen, the purpose of this study was to investigate whether increased oxygen tension increases cell death compared with normoxic conditions (21 kPa oxygen).


METHODS
The effect of hyperoxia on PDT and lipid peroxidation was investigated in two human colon carcinoma cell lines, SW480 and WiDr, and one rat bladder cell carcinoma, AY-27. The cells were incubated with 2 mM 5-aminolaevulinic acid (5-ALA) for 3.5 h at 37 degrees C. This treatment induces the accumulation of protoporphyrin IX (PpIX), which is a potent photosensitizer. PpIX absorbs light energy and produces singlet oxygen in the presence of molecular oxygen, which then destroys the cancer cells. The cells were illuminated (0.5-30 min) at room temperature by blue light (435 nm) prior to hyperoxia exposure. This treatment was performed in a small, temperature-controlled (37 degrees C) hyperbaric chamber using oxygen at a pressure of 100, 200, 300, or 400 kPa.


RESULTS
PDT performed under normoxia induced lipid peroxidation and caused a considerable decrease in cell survival. However, this decrease was not influenced by the presence of hyperoxia (P>0.05). Furthermore, hyperoxic exposure (400 kPa O2) alone caused no increase in lipid peroxidation compared with untreated control cells.


CONCLUSIONS
These data indicate that a normoxic environment is sufficient to produce the optimal effect of PDT.
Hjelde
Astrid
A
Department of Circulation and Imaging, Norwegian University of Science and Technology, Trondheim, Norway. astrid.hjelde@ntnu.no
Gederaas
Odrun A
OA
Krokan
Hans E
HE
Brubakk
Alf O
AO
D000622:Aminolevulinic Acid / Q000008:administration & dosage; D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism*; D015227:Lipid Peroxidation; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000008:administration & dosage; D011524:Protoporphyrins / Q000008:administration & dosage; D051381:Rats; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology
D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX