Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1987 Nov;56(5):589–595. doi: 10.1038/bjc.1987.246

Destruction of erythroleukaemic cells by photoactivation of endogenous porphyrins.

Z Malik 1, H Lugaci 1
PMCID: PMC2001902  PMID: 3480752

Abstract

Selective destruction of Friend erythroleukaemic cells (FELC) was potentiated by stimulation of endogenous porphyrin synthesis followed by light sensitization. Endogenous porphyrin biosynthesis in FELC was induced by supplementation of 5-amino levulinic acid (5-ALA) at a concentration of 5 X 10(-4) M. The main accumulated product, after 4 days culture, was uroporphyrin, while after 8 days culture the cells were loaded with protoporphyrin, up to 1.5 micrograms 10(-7) cells. Photoirradiation of the cells for 2 min, accumulating endogenous porphyrins, induced cardinal deformations and cell disintegration in greater than 95% of the cells, as examined by scanning electron microscopy (SEM). The photodynamic destruction effects were dependent on cultivation time with 5-ALA. Flow cytometry analysis showed an immediate expansion of cell volume subsequent to irradiation, presumably a consequence of water influx. Transmission electron microscopy (TEM) of photosensitized cells after different time intervals of culture in 5-ALA medium, revealed initial damage to mitochondria and water influx into the nuclear envelope, after 2 days. After 3-4 days in culture the water influx phenomenon was pronounced, chromatin condensation took place and slight rupture of the outer membrane was detected. Cells photosensitized after 5-6 days of culture were completely disintegrated leaving a nuclear remnant and an enormously swollen nuclear envelope. The culture time dependence of the process, showed an interrelationship between the photodynamic effect and porphyrin accumulation sites in cellular compartments. The study presents a specific method for erythroleukaemic cell inactivation.

Full text

PDF
589

Images in this article

593Figure 6
on p.593
590Figure 1
on p.590
592Figure 3
on p.592

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Breitbart H., Malik Z. The effects of photoactivated protoporphyrin on reticulocyte membranes, intracellular activities and hemoglobin recipitation. Photochem Photobiol. 1982 Mar;35(3):365–369. doi: 10.1111/j.1751-1097.1982.tb02575.x. [DOI] [PubMed] [Google Scholar]
  2. Evensen J. F., Sommer S., Moan J., Christensen T. Tumor-localizing and photosensitizing properties of the main components of hematoporphyrin derivative. Cancer Res. 1984 Feb;44(2):482–486. [PubMed] [Google Scholar]
  3. Gamliel H. Optimum fixation conditions may allow air drying of soft biological specimens with minimum cell shrinkage and maximum preservation of surface features. Scan Electron Microsc. 1985;(Pt 4):1649–1664. [PubMed] [Google Scholar]
  4. Kessel D., Chou T. H. Tumor-localizing components of the porphyrin preparation hematoporphyrin derivative. Cancer Res. 1983 May;43(5):1994–1999. [PubMed] [Google Scholar]
  5. Kessel D. Localization and photosensitization of murine tumors in vivo and in vitro by a chlorin-porphyrin ester. Cancer Res. 1986 May;46(5):2248–2251. [PubMed] [Google Scholar]
  6. Kessel D. Sites of photosensitization by derivatives of hematoporphyrin. Photochem Photobiol. 1986 Oct;44(4):489–493. doi: 10.1111/j.1751-1097.1986.tb04697.x. [DOI] [PubMed] [Google Scholar]
  7. Land E. J. Porphyrin phototherapy of human cancer. Int J Radiat Biol Relat Stud Phys Chem Med. 1984 Sep;46(3):219–223. doi: 10.1080/09553008414551331. [DOI] [PubMed] [Google Scholar]
  8. Laskey J. D., Ponka P., Schulman H. M. Control of heme synthesis during Friend cell differentiation: role of iron and transferrin. J Cell Physiol. 1986 Nov;129(2):185–192. doi: 10.1002/jcp.1041290209. [DOI] [PubMed] [Google Scholar]
  9. Malik Z., Djaldetti M. 5-Aminolevulinic acid stimulation of porphyrin and hemoglobin synthesis by uninduced Friend erythroleukemic cells. Cell Differ. 1979 Jun;8(3):223–233. doi: 10.1016/0045-6039(79)90049-6. [DOI] [PubMed] [Google Scholar]
  10. Malik Z., Djaldetti M. Destruction of erythroleukemia, myelocytic leukemia and Burkitt lymphoma cells by photoactivated protoporphyrin. Int J Cancer. 1980 Oct 15;26(4):495–500. doi: 10.1002/ijc.2910260415. [DOI] [PubMed] [Google Scholar]
  11. Malik Z., Halbrecht I., Djaldetti M. Regulation of hemoglobin synthesis, iron metabolism, and maturation of Friend leukemic cells by 5-amino levulinic acid and hemin. Differentiation. 1979;13(2):71–79. doi: 10.1111/j.1432-0436.1979.tb01569.x. [DOI] [PubMed] [Google Scholar]
  12. Marks P. A., Rifkind R. A. Erythroleukemic differentiation. Annu Rev Biochem. 1978;47:419–448. doi: 10.1146/annurev.bi.47.070178.002223. [DOI] [PubMed] [Google Scholar]
  13. Moan J., Vistnes A. I. Porphyrin photosensitization of proteins in cell membranes as studied by spin-labelling and by quantification of DTNB-reactive SH-groups. Photochem Photobiol. 1986 Jul;44(1):15–19. doi: 10.1111/j.1751-1097.1986.tb03558.x. [DOI] [PubMed] [Google Scholar]
  14. Pottier R. H., Chow Y. F., LaPlante J. P., Truscott T. G., Kennedy J. C., Beiner L. A. Non-invasive technique for obtaining fluorescence excitation and emission spectra in vivo. Photochem Photobiol. 1986 Nov;44(5):679–687. doi: 10.1111/j.1751-1097.1986.tb04726.x. [DOI] [PubMed] [Google Scholar]
  15. Rimington C., Sommer S., Moan J. Hematoporphyrin ethers--I. Generalized synthesis and chemical properties. Int J Biochem. 1987;19(4):315–320. doi: 10.1016/0020-711x(87)90004-8. [DOI] [PubMed] [Google Scholar]
  16. Rubino G. F., Rasetti L. Porphyrin metabolism in human neoplastic tissues. Panminerva Med. 1966 Jul-Aug;8(7):290–292. [PubMed] [Google Scholar]
  17. Salet C. Hematoporphyrin and hematoporphyrin-derivative photosensitization of mitochondria. Biochimie. 1986 Jun;68(6):865–868. doi: 10.1016/s0300-9084(86)80102-x. [DOI] [PubMed] [Google Scholar]
  18. Sassa S. Sequential induction of heme pathway enzymes during erythroid differentiation of mouse Friend leukemia virus-infected cells. J Exp Med. 1976 Feb 1;143(2):305–315. doi: 10.1084/jem.143.2.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Van Steveninck J., Tijssen K., Boegheim J. P., Van der Zee J., Dubbelman T. M. Photodynamic generation of hydroxyl radicals by hematoporphyrin derivative and light. Photochem Photobiol. 1986 Dec;44(6):711–716. doi: 10.1111/j.1751-1097.1986.tb05528.x. [DOI] [PubMed] [Google Scholar]
  20. Woodcock C. L., Frado L. L., Rattner J. B. The higher-order structure of chromatin: evidence for a helical ribbon arrangement. J Cell Biol. 1984 Jul;99(1 Pt 1):42–52. doi: 10.1083/jcb.99.1.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Zucker R. M., Wu N. C., Mitrani A., Silverman M. Cell volume decrease during Friend leukemia cell differentiation. J Histochem Cytochem. 1979 Jan;27(1):413–416. doi: 10.1177/27.1.438503. [DOI] [PubMed] [Google Scholar]
  22. el-Far M. A., Pimstone N. R. Selective in vivo tumor localization of uroporphyrin isomer I in mouse mammary carcinoma: superiority over other porphyrins in a comparative study. Cancer Res. 1986 Sep;46(9):4390–4394. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES