Role of thromboxane and prostacyclin release on photodynamic therapy-induced tumor destruction.
Thromboxane and prostacyclin levels in serum were measured following photodynamic therapy (PDT) to assess the role of these vasoactive agents on vascular damage and tumor destruction. Sprague Dawley rats were given injections i.v. of Photofrin II doses ranging from 0 to 25 mg/kg. Twenty-four h later, the right hindlimbs of animals bearing chondrosarcoma tumor or controls were exposed to 0-135 J/cm2 630 nm light. Serum concentrations of thromboxane and prostacyclin were determined by radioimmunoassay. A dose-response relationship was established between the amount of photosensitizer administered and the light dose delivered with the release of thromboxane immediately following PDT. Treatment of tumor induced higher levels of thromboxane than did the treatment of tumor-free tissue, suggesting that tumor is more sensitive to PDT-induced damage. The porphyrin and light doses found to induce the release of thromboxane into serum were the same as those required to evoke vascular stasis and tumor destruction. Prostacyclin release was not altered by PDT. The administration of indomethacin (10 mg/kg, i.p.) 3 h before light treatment was found to suppress the intravascular release of thromboxane at the highest porphyrin and light doses studied. Indomethacin treatment also inhibited PDT-induced vascular stasis and tumor destruction, suggesting that the release of thromboxane is linked to these events. Since prostacyclin levels in serum were unchanged following PDT treatment of tumor and controls, thromboxane release appears to be a specific response to PDT and may mediate the vascular stasis observed following PDT.
Fingar
V H
VH
Department of Surgery, University of Louisville, Kentucky 40292.
Wieman
T J
TJ
Doak
K W
KW
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D017323:Dihematoporphyrin Ether; D004305:Dose-Response Relationship, Drug; D004727:Endothelium / Q000187:drug effects; D011464:Epoprostenol / Q000378:metabolism*; D005260:Female; D006415:Hematoporphyrins / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D010778:Photochemotherapy; D051381:Rats; D011919:Rats, Inbred Strains; D013931:Thromboxanes / Q000378:metabolism*
D006415:Hematoporphyrins; D013931:Thromboxanes; D017323:Dihematoporphyrin Ether; D011464:Epoprostenol; D007213:Indomethacin