Comparative sensitivity of microvascular endothelial cells, fibroblasts and tumor cells after in vitro photodynamic therapy with meso-tetra-hydroxyphenyl-chlorin.
The phototoxic effect of meso-tetra-hydroxyphenyl-chlorin (mTHPC)-mediated photodynamic therapy (PDT) on human microvascular endothelial cells (hMVEC) was compared with that on human fibroblasts (BCT-27) and two human tumor cell lines (HMESO-1 and HNXOE). To examine the relationship between intrinsic phototoxicity and intracellular mTHPC content, we expressed cell survival as a function of cellular fluorescence. On the basis of total cell fluorescence, HNXOE tumor cells were the most sensitive and BCT-27 fibroblasts the most resistant, but these differences disappeared after correcting for cell volume. Endothelial cells were not intrinsically more sensitive to mTHPC-PDT than tumor cells or fibroblasts. Uptake of mTHPC in hMVEC increased linearly to at least 48 h, whereas drug uptake in the other cell lines reached a maximum by 24 h. No difference in drug uptake was seen between the cell lines during the first 24 h, but by 48 h hMVEC had a 1.8- to 2.8-fold higher uptake than other cell lines. Endothelial cells showed a rapid apoptotic response after mTHPC-mediated PDT, whereas similar protocols gave a delayed apoptotic or necrotic like response in HNXOE. We conclude that endothelial cells are not intrinsically more sensitive than other cell types to mTHPC-mediated PDT but that continued drug uptake beyond 24 h may lead to higher intracellular drug levels and increased photosensitivity under certain conditions.
Triesscheijn
Martijn
M
Division of Experimental Therapy (H6), The Netherlands Cancer Institute/Antoni van Leeuwenhoek Ziekenhuis, 1066 CXAmsterdam, The Netherlands.
Ruevekamp
Marjan
M
Aalders
Maurice
M
Baas
Paul
P
Stewart
Fiona A
FA
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000528:radiation effects*; D005347:Fibroblasts / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D008652:Mesoporphyrins / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D009369:Neoplasms / Q000473:pathology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D013997:Time Factors
D000970:Antineoplastic Agents; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin