The photodynamic effects of photofrin II, hematoporphyrin derivative, hematoporphyrin, and tetrasodium-mesotetra(4-sulfonatophenyl)porphine in vitro: clonogenic cell survival and drug uptake studies.
The human colon adenocarcinoma cell line, WiDr, was exposed to Photofrin II, hematoporphyrin derivative (HPD), hematoporphyrin (HP) or tetrasodium-meso-tetra(4-sulfonatophyenyl)porphine (TPPS4) followed by irradiation with light. Clonogenicity was determined and the resultant survival curves compared and shown to be qualitatively similar in shape. However, for equal amounts of drug in the medium, there were large differences in photosensitizing efficiency with Photofrin II approximately 5, 25 and 50 fold more effective than HPD, HP and TTPS4, respectively. For the same power used, all drugs were less efficient photosensitizers under red light (600-1100 nm) than under white light (300-110 nm). For all drugs this could be explained in terms of changes in light absorption over the two wavelength ranges. Differences in clonogenic cell survival could not be explained in terms of differences in singlet oxygen production (from published values). A reduction in drug uptake into the cells was sufficient to explain the differences between Photofrin II, HPD and HP, while TPPS4 was 5-fold less effective compared to other drugs than would be expected from drug uptake measurements. Two methods for measuring drug uptake were compared and shown to give different results for Photofrin II. Measurements of drug fluorescence in 0.1 N NaOH yielded 5-fold lower values than when measurements were in 1 N HCl following heat treatment to monomerise aggregated drug. Clearly the reliability of the method used in determining drug uptake must be carefully ascertained.
West
C M
CM
Moore
J V
JV
D000230:Adenocarcinoma; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects* / Q000528:radiation effects; D003110:Colonic Neoplasms; D003114:Colony-Forming Units Assay; D017323:Dihematoporphyrin Ether; D017324:Hematoporphyrin Derivative; D006415:Hematoporphyrins / Q000494:pharmacology*; D006801:Humans; D008027:Light; D011166:Porphyrins / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
D006415:Hematoporphyrins; D011166:Porphyrins; D011838:Radiation-Sensitizing Agents; C016136:tetraphenylporphine sulfonate; D017324:Hematoporphyrin Derivative; D017323:Dihematoporphyrin Ether