Effects of photodynamic therapy on xenografts of human mesothelioma and rat mammary carcinoma in nude mice.
We have examined the effectiveness of photodynamic therapy against R3230AC rat mammary adenocarcinoma and human mesothelioma as xenografts in the same host. The results demonstrate that the xenografted human tumour is significantly more responsive to photodynamic treatment than the rodent mammary tumour. Studies also showed that the mesothelioma xenograft was fluence rate- and fluence-dependent while the rat tumour exposed to the same conditions demonstrated neither of these dependencies. This disparity in response was not attributable to a difference in either whole-tumour uptake or subcellular distribution of the porphyrin photosensitiser. Analysis of the effects of visible irradiation on cytochrome c oxidase activity, measured in mitochondria prepared from tumours borne on hosts injected with photosensitiser, demonstrated that photoradiation-induced enzyme inhibition was significantly greater in mesothelioma than in R3230AC mammary tumour preparations. However, in parallel studies conducted in vitro, when photosensitiser and light were delivered to previously unperturbed mitochondria, rates of enzyme inhibition were not significantly different. Both tumours were established in long-term cell culture. While the uptake of porphyrin photosensitiser was equivalent in both cell lines, the R3230AC cells displayed a significantly greater photosensitivity than the mesothelioma cells. The data presented here demonstrate that the mechanisms that govern response to photodynamic therapy are complex, but in the case of these two xenografted tumours host response to therapy is not likely to play a significant role.
Gibson
S L
SL
Department of Biochemistry, University of Rochester, School of Medicine and Dentistry, New York 14642.
Foster
T H
TH
Feins
R H
RH
Raubertas
R F
RF
Fallon
M A
MA
Hilf
R
R
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D017323:Dihematoporphyrin Ether / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006415:Hematoporphyrins / Q000378:metabolism; D006801:Humans; D008027:Light; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008654:Mesothelioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D008928:Mitochondria / Q000378:metabolism / Q000528:radiation effects; D010778:Photochemotherapy; D051381:Rats; D014018:Tissue Distribution; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D006415:Hematoporphyrins; D017323:Dihematoporphyrin Ether