TY - JOUR
T1 - Cellular uptake, localization and photodynamic effects of haematoporphyrin derivative in human glioma and squamous carcinoma cell lines
AU - Gupta, Seema
AU - Dwarakanath, B. S.
AU - Muralidhar, K.
AU - Jain, V.
N1 - Funding Information:
Thanks are due to Dr. N.K. Chaudhury, Mr. J.S. Adhikari and Dr. Sudhir Chandna for help in spectroscopic, flow cytometric and image analysis studies. We are grateful to Maj. Gen. T. Ravindranath, Director, INMAS and Dr. T. Lazar Mathew, former Director for their interest and support for this work. S.G. was a recipient of a research fellowship from the University Grants Commission and CSIR, Govt. of India.
PY - 2003/2
Y1 - 2003/2
N2 - 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).
AB - 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).
KW - Apoptosis
KW - Cytogenetic damage
KW - Haematoporphyrin derivative
KW - Intracellular localization
KW - Photodynamic therapy
KW - p53
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U2 - 10.1016/S1011-1344(02)00408-6
DO - 10.1016/S1011-1344(02)00408-6
M3 - Review article
C2 - 12633983
AN - SCOPUS:0037296083
SN - 1011-1344
VL - 69
SP - 107
EP - 120
JO - Journal of Photochemistry and Photobiology B: Biology
JF - Journal of Photochemistry and Photobiology B: Biology
IS - 2
ER -