Inhibition of Cellular DNA Synthesis and Lack of Antileukemic Activity by Non-Photoactivated Hematoporphyrin Derivative

Abstract

It has been reported that cytocidal activity of light-activated hematoporphyrin (HPD) within the cells might be exploited in the therapy of experimental and human cancer. As part of a project from this laboratory aimed to study some major biologic features of HPD, it was found that [³H]thymidine incorporation in tumor cells was highly inhibited as a consequence of HPD treatment. HPD-mediated inhibition, obtained by a treatment either in vitro or in vivo, was long lasting and independent of light activation. Cellular DNA synthesis was inhibited by non toxic doses of HPD which were not influential either cell viability or cell oncogenicity. In preliminary studies, HPD-treated cells accumulated in the G₁ phase of the cell cycle as detected by cytofluorometric analysis. This finding is in keeping with a likely inhibition exerted in late G, or at the beginning of the S phase of cell the cycle and might exclude a direct damage of the DNA synthetic machinery. Definitive loss of cell viability and cellular DNA inhibition was obtained immediately after the exposure of HPD-treated cells to He-Ne laser light. HPD-mediated cell lysis was dose dependent and in the order of magnitude of cytocidal doses in different cell systems. HPD antileukemic activity or HPD interactions with chemotherapeutic drugs was ruled out in L1210 leukemic mice.