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 R32 30AC rat mammary adenocarcinoma and human mesothelioma as xenografts i n the same host. The results demonstrate that the xenografted human tu mour is significantly more responsive to photodynamic treatment than t he rodent mammary tumour. Studies also showed that the mesothelioma xe nograft was fluence rate- and fluence-dependent while the rat tumour e xposed to the same conditions demonstrated neither of these dependenci es. This disparity in response was not attributable to a difference in either whole-tumour uptake or subcellular distribution of the porphyr in 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 tha t photoradiation-induced enzyme inhibition was significantly greater i n mesothelioma than in R3230AC mammary tumour preparations. However, i n parallel studies conducted in vitro, when photosensitiser and light were delivered to previously unperturbed mitochondria, rates of enzyme inhibition were not significantly different. Both rumours were establ ished in long-term cell culture. While the uptake of porphyrin photose nsitiser was equivalent in both cell lines, the R3230AC cells displaye d 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 pla y a significant role.