Photodynamic effects of haematoporphyrin derivative on synchronized and asynchronous cells of different origin

Christensen, Terje; Feren, Kari; Moan, Johan Emelian; Pettersen, Erik O.

doi:10.1038/bjc.1981.258

Cited by 32 publications

(11 citation statements)

References 22 publications

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“…The uptake of HpD and the resulting photosensitivity are generally found to be similar in transformed and normal cells in vitro (Chang & Dougherty 1978;Christensen et al, 1981;. The present study indicates that a slightly higher amount of HpD is strongly retained in the transformed cells of type III (Table I).…”

Section: Discussionsupporting

confidence: 68%

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

Christensen¹,

Sandquist²,

Feren³

et al. 1983

Br J Cancer

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Section: Discussionsupporting

confidence: 68%

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

Christensen¹,

Sandquist²,

Feren³

et al. 1983

Br J Cancer

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“…This is supported by the similarity in drug uptake between exponentially growing and plateauphase cells (Table I). In contrast to the results of Christensen et al (1981), Gomer & Smith (1980) showed no cell cycle response, further supporting the notion of cell line dependent, growth phase related differences.…”

Section: Discussioncontrasting

confidence: 54%

“…There is an increase in the proportion of G1-like cells with increasing WiDr culture age from 68 (day 6 cultures) to 78% (day 12) (15% increase (West et al, 1988)). It has been shown that, for some cell lines, G1 cells are the most resistant of cells in the cell cycle to photodynamic treatment (Christensen et al, 1981). It is possible that WiDr cells show a variable cell cycle response with G1 resistance and that the increase in proportion of G1 cells in plateau-phase cultures accounts for resistance to PDT.…”

Section: Discussionmentioning

confidence: 99%

Size-dependent resistance of human tumour spheroids to photodynamic treatment

West

1989

Br J Cancer

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Summary Spheroids derived from the human colon adenocarcinoma cell line, WiDr, were exposed to lOpgmlPl Photofrin II and irradiated with light (700nm, 5OmWcm-2). Compared with exponentially growing monolayer cultures, cells in spheroids of 100, 250 and 500um diameter were respectively 1.8, 2.5 and 22-fold less sensitive. The small resistance of plateau-phase cultures (1.3-fold) was insuflicient to account for this marked spheroid size-dependent resistance. For monolayer cultures and for spheroids of 100 and 250pm diameter, the results were the same whether irradiations were carried out pre-or post-trypsinisation. However, there was a difference for the largest spheroid size: when irradiations were carried out pre-trypsinisation, spheroids were more resistant than when irradiations were given post-trypsinisation. Drug extraction studies showed that there was no difference in the average drug uptake between cultures of exponentially growing or plateau-phase cells, and lOOpm diameter spheroids while 250 and 500pm diameter spheroids took up proportionally 0.5 and 0.4 as much drug. Cell contact effects, drug heterogeneity between cells, hypoxia and problems in drug penetration are suggested as possible reasons for the resistance of large spheroids to photodynamic treatment.During the past decade there has been increasing interest in the potential of photodynamic therapy (PDT) as a new modality for the treatment of cancer. Although many of the factors determining response have been investigated, there are still many areas of the biology of PDT yet to be studied. The use of multicellular spheroids as a tool for the investigation of tumour response to other therapies is well established. They are useful, for example, for assessing the contribution of hypoxia (Sutherland et al., 1970;West et al., 1984; West & Sutherland, 1987), diffusion limitations (Sutherland et al., 1979;Durand, 1981), cell contact effects (Durand & Sutherland, 1972;West & Stratford, 1987), and repair processes (Durand & Sutherland, 1972;West et al., 1984) in the response of cells to a particular treatment.The resistance of spheroids to photodynamic treatment has been documented previously (Christensen et al., 1984). However, to date, there has been no systematic study of the effect of spheroid size on the development of this resistance. In addition, there have been conflicting reports of the effect of cell growth phase on sensitivity to photodynamic treatment. Christensen et al. (1984) reported that log-and plateau-phase NHIK 3025 cells were equally sensitive to haematoporphyrin derivative (HPD) plus light, while BenHur et al. (1987) showed that V79 cells in the plateau-phase of growth were more sensitive than exponentially growing cells to photosensitisation with chloroaluminium phthalocyanine.The following work describes a study of the effect of spheroid size on photosensitisation by Photofrin II. In addition, the role of the growth phase of cells during drug exposure has been investigated. The end-point used was clonogenic cell survival. Spheroid...

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“…The response of a cell to PDT may vary with its position in the cell cycle (7). This could lead to colonies with different sensitivity to PDT provided that a significant degree of synchrony existed within the colonies.…”

Section: Methodsmentioning

confidence: 99%

Cooperative effects of photodynamic treatment of cells in microcolonies

Dahle

Kaalhus

Moan

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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Microcolonies of 2-8 Madison-Darby canine kidney cells (MDCK II) and Chinese hamster lung fibroblasts (V79) cells were incubated with the photosensitizer Photofrin and exposed to light, and the resulting number of dead cells per colony was determined. The distribution of this number was found to be incompatible with the assumption that cells are inactivated independently. The experimental distributions were significantly different from the binomial distribution expected from this assumption, but in accordance with a model in which an inactivated cell can inactivate adjacent cells with a certain probability. These findings are contrary to the common view that damage caused by radiation is limited to the cell in which the primary damage takes place. Our findings clearly indicate some kind of cooperativity between cells treated with Photofrin and light.

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Photodynamic effects of haematoporphyrin derivative on synchronized and asynchronous cells of different origin

Cited by 32 publications

References 22 publications

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

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

Size-dependent resistance of human tumour spheroids to photodynamic treatment

Cooperative effects of photodynamic treatment of cells in microcolonies

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