Inability to elicit rapid cytocidal effects on L1210 cells derived from porphyrin-injected mice following in vitro photoirradiation.

The role of the neoplastic cell in both porphyrin localization and the photochemotherapeutic response was investigated with the use of a series of tumor-localizing porphyrins and the L1210 tumor system. In vivo photoirradiation of DBA/2Ha mice bearing L1210 solid tumors and previously given injections of meso-tetra-(4-sulfonatophenyl)-porphine, meso-tetra-(4-carboxyphenyl)-porphine, or hematoporphyrin derivative (Hpd) indicated that all three chemicals elicited a photodynamic response resulting in necrosis of exposed tissue. Isolation of tumor cells from mice given injections of porphyrin with the use of mild mechanical means and physiologic conditions followed by in vitro photoirradiation of the cells under conditions established to optimize rapid cytocidal effects resulted in no appreciable cell death. A similar situation was noted with the use of spleen cells from mice given injections of Hpd, the spleen cells presumably containing substantial amounts of porphyrin. Both fluorescence microscopy and chemical extraction and quantitation of the porphyrins in the cells indicated that the inability to elicit a rapid cytocidal effect upon in vitro photoirradiation resulted from either the absence of or the presence of only very small amounts of porphyrin. These results indicate that in this particular tumor system the neoplastic cell per se plays only a minor role in porphyrin localization and, as a consequence, cannot be readily killed upon photoirradiation, suggesting that rapid cytocidal effects, due solely to porphyrin contained within the cell, probably do not occur among the majority of parenchymal cells during in vivo photoirradiation.