Photochemotherapy of tumours with mesotetrahydroxyphenyl chlorin is pH dependent.
Human colon carcinoma cells of the WiDr line were incubated with the tumour-localizing and photosensitizing drug mesotetrahydroxyphenyl chlorin (mTHPC) at either pH 6.8, 7.2 or 7.8. The cellular uptake of the drug was found to be independent of the pH value. However, under conditions where the cells contained the same amount of the drug (i.e. after incubation at different pH values) and were exposed to light, their photosensitivity increased with decreasing pH value. Furthermore, the cells were more photosensitive at 4 degrees C than at 37 degrees C. The shoulder on the survive curves, observed for irradiation at 37 degrees C and at pH 7.2-7.8 was practically absent for irradiation at 4 degrees C and even at 37 degrees C when the light exposure took place at pH 6.8. The observations may be related to a reduced repair of photochemotherapy (PCT)-induced damage at 4 degrees C and at pH 6.8. The high PCT efficiency at pH 6.8 may contribute to the tumour selectivity of PCT with mTHPC.
Ma
L W
LW
Department of Biophysics, Institute for Cancer Research, Oslo, Norway.
Bjørklund
E
E
Moan
J
J
D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008652:Mesoporphyrins / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D013696:Temperature
D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin