Cellular uptake, localization and photodynamic effects of haematoporphyrin derivative in human glioma and squamous carcinoma cell lines.
Uptake, intracellular concentration, localization and photodynamic effects of a haematoporphyrin derivative (HpD, Photosan-3) were compared in human glioma (BMG-1, wild-type p53) and squamous carcinoma (4451, mutated p53) cell lines. Concentration and time dependence of cellular uptake of HpD was assayed from methanol extracts and whole cell suspension spectroscopy, while localization was studied by fluorescence microscopy-based image analysis. Colony-forming ability, apoptosis, cell-cycle progression and cytogenetic damage (micronuclei formation) were investigated as parameters of photodynamic response following irradiation with red light. BMG-1 cells were more sensitive to the photodynamic treatment than 4451 cells, although the 4451 cells accumulated a higher amount of HpD and did not differ significantly from BMG-1 cells with respect to intracellular localization. Photodynamically-induced cytogenetic damage and apoptosis were considerably higher in BMG-1 cells as compared to 4451 cells. The present results strongly suggest that manifestation of the photodynamically-induced lesions in the form of cytogenetic damage and apoptosis are among the important determinants of cellular sensitivity to HpD-PDT besides the photodynamic dose (intracellular concentration of the photosensitizer and the light dose).
Gupta
Seema
S
Department of Biocybernetics, Institute of Nuclear Medicine and Allied Sciences, Brig SK Mazumdar Road, Timarpur, Delhi 110054, India.
Dwarakanath
B S
BS
Muralidhar
K
K
Jain
V
V
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D004305:Dose-Response Relationship, Drug; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D006415:Hematoporphyrins; D006801:Humans; D008027:Light; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000528:radiation effects; D015162:Micronucleus Tests; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects
D006415:Hematoporphyrins; D017319:Photosensitizing Agents; C071875:photosan III