In vitro effects and localisation of the photosensitizers m-THPC and m-THPC MD on carcinoma cells of the human breast (MCF-7) and Chinese hamster fibroblasts (V-79).
OBJECTIVE
Photodynamic therapy (PDT) is the combination of a photosensitizer with laser light to induce preferential destruction of malignant cells. In this study two new photosensitizers--5,10,15,20-meta-tetra(hydroxyphenyl) chlorin (m-THPC) and m-THPC MethoxyPEG2000 derivative (m-THPC MD)--were tested, both for their dark toxicity, i.e., cytotoxicity in the absence of light, and for their light-induced cytotoxicity in mammalian cell cultures.


METHODS
Cell lines used were MCF-7 (human breast carcinoma) and V-79 (Chinese hamster lung fibroblast). After cultivation under standard conditions, cells were administered the photosensitizers and 24 hr later exposed to various energy levels of laser light at a wavelength of 652 nm. Cell survival was monitored using a clonogenic assay and was expressed as the surviving fraction of the untreated control.


RESULTS
Up to an m-THPC concentration of 1 microgram/ml, no dark toxicity was observed; at higher concentrations a rapid fall in survival occurred. m-THPC MD showed no dark toxicity up to 100 micrograms/ml. In vitro m-THPC was approximately 10 times more cytotoxic than m-THPC MD. The MCF-7 and V-79 cell lines displayed similar responses to PDT.


CONCLUSIONS
Both m-THPC and m-THPC MD are very efficient photosensitizers in vitro. Up to the therapeutic dose, neither exhibited dark toxicity. There is clinical relevance of the photosensitizers by a large therapeutic index.
Hornung
R
R
Department of Gynecology and Obstetrics, University Hospital, Zurich, Switzerland.
Jentsch
B
B
Crompton
N E
NE
Haller
U
U
Walt
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D006801:Humans; D007834:Lasers; D008652:Mesoporphyrins / Q000494:pharmacology*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D008652:Mesoporphyrins; D017319:Photosensitizing Agents; C072269:temoporfin