Characterization of photodynamic effects of meso-tetrakis-(4-methoxyphenyl) porphyrin: biological consequences in a human carcinoma cell line

The photodynamic behavior of 5,10,15,20-tetrakis(4-methoxyphenyl)porphyrin (TMP) has been investigated in solutions containing photo-oxidizable substr ates and in the presence of Hep-2 human larynx-carcinoma cell line. It has been found that Hep-2 cells rapidly incorporate TMP until an intracellular concentration of similar to0.018 mu mol of TMP/10(6) cells is reached. The survival of the irradiated cells treated with TMP was dependent upon both l ight exposure level and intracellular sensitizer concentration. In addition , a linear dependence of the photoinactivation rate (1/D-50, where D-50 rep resents the light exposure level required to inactivate 50% of the cell pop ulation) and TMP intracellular concentration was found, indicating that TMP localizes at unsaturated sites within the cells. TMP photosensitized singl et molecular oxygen ((1)Delta (2)) with a quantum yield of 0.65. When the a mino acid L-tryptophan was used to assess (1)Delta (2)-mediated photooxidat ion in a homogeneous medium, singlet molecular oxygen ((1)Delta (g)) mediat ion appeared to be mainly responsible for the cell inactivation. These in v itro results enhance our understanding of the phototoxicity of porphyrins i n cellular media and the sensitivity of Hep-2 cells to photodamage. (C) 200 1 Elsevier Science Ltd. All rights reserved.