A comet assay of DNA damage and repair in K562 cells after photodynamic therapy using haematoporphyrin derivative, methylene blue and meso-tetrahydroxyphenylchlorin

McNair, Fiona I.; Marples, Brian; West, Catharine M L; Moore, James

doi:10.1038/bjc.1997.295

Cited by 55 publications

(33 citation statements)

References 31 publications

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“…Since our data are in contrast to in-vitro studies in human myeloid leukaemia and nasopharyngeal carcinoma cells where no DNA damage was found after mTHPC-PDT [33,34], the observed effect may depend on cell line.…”

Section: Discussioncontrasting

confidence: 54%

Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro

Gyenge

Hiestand

Graefe

et al. 2011

Photodiagnosis and Photodynamic Therapy

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BACKGROUND: Meso-tetra-hydroxyphenyl-chlorine (mTHPC) is among the most powerful photosensitizers available for photodynamic therapy (PDT). However, the mechanisms leading to cell death are poorly understood. We here focused on changes at DNA and RNA levels after treatment with the liposomal mTHPC derivative Foslipos in vitro. METHODS: After determination of darktoxicity, laser conditions and uptake kinetics, PC-3 prostate carcinoma cells were subjected to PDT with Foslipos, followed by assessment of cell numbers directly (TP0) or 1h (TP1), 2h (TP2), 5h (TP5) and 24h (TP24) after illumination. Nucleic acids had been extracted for evaluation of RNA amounts and integrity as well as for estimation of abasic sites as a measure for DNA damage. Furthermore, expression changes of 84 genes related to oxidative stress were investigated by quantitative polymerase chain reaction. RESULTS: Already at TP0, the number of dead cells was significantly higher after PDT versus controls and at TP24 more than 90% of cells had been destroyed. PDT resulted in a severe damage of both RNA and DNA. Gene expression analyses revealed an impact of PDT on pathways for oxidative and metabolic stress, heat shock, proliferation and carcinogenesis, growth arrest, inflammation, DNA repair and apoptosis signaling. CONCLUSIONS: Mechanisms of Foslipos-mediated PDT comprise a combination of acute and delayed lethal effects in PC-3 cells. The latter may include death processes initiated by nucleic acid damage, activation of stress and growth arrest genes in combination with a reduced capability to adequately cope with oxidative toxicity. Our results will help to better understand molecular photodynamic effects. AbstractBackground: Meso-tetra-hydroxyphenyl-chlorine (mTHPC) is among the most powerful

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Section: Discussioncontrasting

confidence: 54%

Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro

Gyenge

Hiestand

Graefe

et al. 2011

Photodiagnosis and Photodynamic Therapy

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“…Oxidative damage leading to single-strand breaks and alkali-labile sites, DNA-protein crosslinks and DNA degradation, as well as to chromosome aberrations has been reported (Evans et al, 1997; Oleinick and Evans, 1998). These lesions, however, are likely to be relatively easily repaired (McNair et al, 1997). Considering that MMR seems not to be affected by PDT, it is reasonable to assume that PDTinduced DNA damage remains of low clinical importance.…”

Section: Discussionmentioning

confidence: 99%

“…5,10,15,20-meta-tetra-(hydroxyphenyl)chlorin (m-THPC) is a neutral lipophilic second-generation photosensitiser with an absorption maximum at 652 nm. Confocal laser scanning fluorescence microscopy studies of m-THPC in vitro have shown a diffuse distribution of the drug in the cytoplasm (McNair et al, 1997). Although there is no localisation of the photosensitiser within the nucleus, a low level of potentially mutagenic DNA damage could occur, depending on the photosensitiser, the cellular repair mechanisms and the affected genes (Oleinick and Evans, 1998).…”

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confidence: 99%

Photodynamic therapy of DNA mismatch repair-deficient and -proficient tumour cells

et al. 2002

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Loss of DNA mismatch repair is a common finding in hereditary nonpolyposis colon cancer as well as in many types of sporadic human tumours. DNA mismatch repair-deficient cells have been reported to be resistant to many chemotherapeutic agents and to radiotherapy, and to have the potential of rapidly acquiring additional mutations leading to tumour progression. Photodynamic therapy is a new treatment modality using light to activate a photosensitiser that preferentially localises in tumour cells. An oxygen dependent photochemical reaction ensues, resulting in selective tumour necrosis. The effect of loss of DNA mismatch repair activity on the sensitivity to photodynamic therapy was tested using pairs of cell lines proficient or deficient in mismatch repair due to loss of either MLH1 or MSH2 protein function. Cells were incubated with the photosensitiser 5,10,15,20-meta-tetra(hydroxyphenyl)chlorin and exposed to laser light at 652 nm with various optical doses ranging from 0 -1 J cm 72 . Cell survival was assessed using the clonogenic assay. Loss of MLH1 or MSH2 function was not associated with resistance to photodynamic therapy. MCF-7 cells repeatedly treated with photodynamic therapy expressed parental levels of MLH1, MSH2, MSH6, and PMS2. DNA mismatch repair-deficient and -proficient cells showed similar subcellular distributions of meta-tetra(hydroxyphenyl)chlorin as analysed by laser scanning and fluorescence microscopy. Therefore, repeated exposure of tumour cells to photodynamic therapy does not seem to result in loss of DNA mismatch repair, and loss of mismatch repair, in turn, does not seem to contribute to resistance to photodynamic therapy. Our results suggest recommending photodynamic therapy as a strategy for circumventing resistance due to loss of DNA mismatch repair.

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“…The mechanisms of DNA damage induced by photodynamic therapy are not well known. PDT can cause cross-linking of DNA strands (McNair et al, 1997, Haylett et al, 2003, Woods et al, 2004. DNA damage caused by photodynamic therapy may occur in cancer cells and normal cells surrounding the tumor.…”

Section: Changes In Dnamentioning

confidence: 99%

Can Photodynamic Therapy Be an Alternative Method in Melanoma Treatment?

Choromańska¹,

Kulbacka²,

Chwiłkowska³

et al. 2011

Treatment of Metastatic Melanoma

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A comet assay of DNA damage and repair in K562 cells after photodynamic therapy using haematoporphyrin derivative, methylene blue and meso-tetrahydroxyphenylchlorin

Cited by 55 publications

References 31 publications

Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro

Cellular and molecular effects of the liposomal mTHPC derivative Foslipos in prostate carcinoma cells in vitro

Photodynamic therapy of DNA mismatch repair-deficient and -proficient tumour cells

Can Photodynamic Therapy Be an Alternative Method in Melanoma Treatment?

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