The effect of tumor localizing porphyrins on the conversion of fibrinogen to fibrin.
The interaction of hematoporphyrin IX and two synthetic porphyrin tumor localizers, meso-tetra (4-carboxyphenyl) porphine (TCPP) and mesotetra (4-sulfonatophenyl) porphine (TPPS4) with fibrinogen was investigated in the presence and absence of light. Both TPPS4 and TCPP were found to bind to fibrinogen in greater than a 1/1 mole ratio in the absence of light. Chromatographic analysis indicated that during illumination TPP4 bound to fibrinogen to a greater extent that did either TCPP or hematoporphyrin. Both TCPP and TPPS4 were found to exhibit a greater inhibitory effect on clotting in the presence of light than did hematoporphyrin. In the absence of light and added Ca2+, both TCPP and TPPS4 were found to stimulate clotting at very specific porphyrin/fibrinogen concentration ratios, with TPPS4 being the more potent stimulator of the two. Hematoporphyrin exhibited little or no effect on clotting times. Fibrinogen, photoirradiated in the presence of the porphyrins was found to inhibit the clotting of unirradiated fibrinogen. A comparison of the stimulatory effects on clotting times by either calcium or TCPP and TPPS4 indicated that the porphyrins were capable of eliciting a greater stimulatory response than did calcium. The magnitude of the stimulatory response caused by the porphyrins alone was substantially reduced in the presence of calcium although the overall stimulatory response was increased but not additive. This suggests some interaction between either the calcium and porphyrin molecules or similarities in the respective stimulatory mechanism(s) involved. A possible correlation between these observations and the porphyrins ability to localize in tumors is also discussed.
D001777:Blood Coagulation / Q000187:drug effects; D005337:Fibrin / Q000378:metabolism*; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000378:metabolism*; D011166:Porphyrins / Q000378:metabolism*; D013997:Time Factors; D014914:Whole Blood Coagulation Time
D011166:Porphyrins; D005337:Fibrin; D005340:Fibrinogen