Destruction of erythroleukemia, myelocytic leukemia and burkitt lymphoma cells by photoactivated protoporphyrin

Abstract

The effect of protoporphyrin on erythroid, myeloid and lymphoid leukemic cells and their destruction induced by the photoactivated porphyrin was studied. Friend erythroleukemic cells (FL) and myelocytic leukemic cells (ML) accumulated protoporphyrin in a cap or patch-like pattern observed by fluorescence microscopy. Photoactivated protoporphyrin induced the appearance of "holes" on the cell membrane demonstrated by scanning electron microscopy. On the other hand, Burkitt lymphoma (BL) and mastocytoma (MS) cells accumulated porphyrin intracellularly around the nuclear envelope and as circular profiles, respectively. Photoactivated protoporphyrin induced development of multiple blebs on the cell membrane, and even complete cell destruction. Cytotoxicity of protoporphyrin at short-term incubation periods was determined by [3H]thymidine and [3H]uridine incorporation. Protoporphyrin, unexposed to light, reduced the incorporation of both precursors only to a moderate extent. On the other hand, porphyrin-treated cells exposed to light showed complete inhibition of RNA and DNA synthesis. Long-term exposure of ML and BL cells to porphyrin in the dark induced a nearly 50% inhibition of RNA and DNA synthesis. Although the cytotoxic effect of protoporphyrin in the dark was lower than that of photoactivated porphyrin, this may possess a potential activity in vivo even without illumination.

Destruction of erythroleukaemic cells by photoactivation of endogenous porphyrins

“…It has been demonstrated that organization of chromatin in relaxed or condensed nucleosome zig-zag fibres is largely dependent on ion concentration (Woodcock et al, 1984). Thus, water influx into the nuclear envelope and nucleus will probably result in DNA synthesis alteration which was described as a general phenomenon in photosensitized cells (Malik & Djaldetti, 1980). Cell lysis was the end phase of porphyrin photosensitization of FELC, an effect similar to that of photoporphyrin on erythrocytes and reticulocytes, while the nucleus was the only remnant from the destroyed FELC.…”

“…On the other hand, it is well known that the natural protoporphyrin is an excellent photosensitizer, inducing haemolysis and light sensitivity of the skin in porphyric patients (Meyer & Schmid, 1978). It is a poor tumour localizer despite its high photo-activity potential on in vitro incubated cells (Malik & Djaldetti, 1980). In addition, protoporphyrin is biosynthesized in low amounts, by all tumour cells, as well as non-transformed tissues, while in specific transformed cells such as erythroleukaemia, it can be produced more efficiently (Marks & Rifkind, 1978).…”

HEMATOPORPHYRIN and HPD: PHOTOPHYSICS, PHOTOCHEMISTRY and PHOTOTHERAPY

“…This damage results in cell lysis (Bellnier and Dougherty, 1982), impairment of transport and permeability parameters (Kessel, 1976), and microscopicallydetectable membrane damage (Malik and Djaldetti, 1980;Volden et al, 1981). The resulting increase in membrane permeability promotes the toxicity of other cytotoxic drugs, e.g.…”

BPD-MA-mediated photosensitization in vitro and in vivo: cellular adhesion and β1 integrin expression in ovarian cancer cells

“…The complex nature of the mechanisms in cell and tissue damage in response to PDT could profoundly influence the metastatic process. Along these lines it was shown that PDT causes cellular membrane damage (Malik and Djaldetti, 1980;Evenson et al, 1984;Moan and Vistnes, 1986), and tumour cells treated with Photofrin® (PF®)-based PDT release compounds such as prostanoids including prostaglandin E 2 (PGE 2 ), prostacyclin, thromboxane (TX) and von Willebrand factor (vWf) (Henderson and Donovan, 1989;Fingar et al, 1990;Foster et al, 1991). PGE 2 has been shown to directly influence the in vivo dissemination and in vitro migration of Lewis lung carcinoma cells (Young et al, 1987), and differences exist in the amount of synthesis of PGE 2 and prostacyclin by normal, tumour and metastatic cells (Young et al, 1987).…”