Retention and photodynamic effects of haematoporphyrin derivative in cells after prolonged cultivation in the presence of porphyrin

Br J Cancer. 1983 Jul;48(1):35-43. doi: 10.1038/bjc.1983.154.

Abstract

Photoradiation therapy of cancer in the presence of haematoporphyrin derivative is based on a retention of porphyrin in malignant tissue. After long term incubation of NHIK 3025 cells in the presence of 25 microgram ml-1 haematoporphyrin derivative, one fraction is easily removed from the cells by washing with a serum-rich medium. Another fraction remains bound to the cells for a prolonged time. The former does not contribute to the photosensitivity of the cells while the latter, the tightly-bound component, results in a photosensitivity proportional to the cellular contents of porphyrin. Transformed cells are shown to be slightly more sensitive and to retain 25-50% more haematoporphyrin derivative than non-transformed cells. Cytological effects of light absorbed by the tightly-bound component have been studied. The growth of treated cells is similar to that of control cells after a dose-dependent post irradiation lag period. A relatively slow leakage of lactate dehydrogenase (LDH) out of the cells takes place after treatment. The treatment induces a significant increase in the frequency of sister chromatid exchanges (SCE). We conclude that photoactivation of the tightly-bound fraction of haematoporphyrin derivative induces less damage to the outer cell membrane and probably more intracellular damage than irradiation of cells after a short period in contact with the derivative.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Division / radiation effects
  • Cell Line
  • Cell Survival / radiation effects
  • Cell Transformation, Neoplastic / metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Radiation
  • Hematoporphyrin Derivative
  • Hematoporphyrins / metabolism*
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Light*
  • Mice
  • Radiation-Sensitizing Agents / metabolism*
  • Sister Chromatid Exchange / radiation effects
  • Time Factors

Substances

  • Hematoporphyrins
  • Radiation-Sensitizing Agents
  • Hematoporphyrin Derivative
  • L-Lactate Dehydrogenase