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

Abstract

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.

Common fragile sites in colon cancer cell lines: Role of mismatch repair, RAD51 and poly(ADP-ribose) polymerase-1

“…This effect was not observed in MMR-deficient cells, in which APC action prevailed. These data are in agreement with the increased CFS expression after replicative stress that was reported in RAD51-depleted MCF-7 breast cancer cells [11], which also happen to be MMR-proficient [54].…”

Measurement of 7,8-dihydro-8-oxo-2′-deoxyguanosine metabolism in MCF-7 cells at low concentrations using accelerator mass spectrometry

“…For example, it has been reported that the oxidized nucleoside triphosphate pool is a significant contributor to genomic instability in mismatched repair-deficient cells (25,26). However, this situation is unlikely for MCF-7 cells because there are reports of mismatch repair proficiency for these cells (27)(28)(29).…”

Toluidine blue O photodynamic inactivation on multidrug‐resistant pseudomonas aeruginosa

“…PDT can inactivate antibiotic-resistant microbial pathogens and has the potential to become an efficient alternative treatment modality for microbial infections [9]. In the field of oncology, PDT has become a promising modality for the treatment of a variety of solid tumors [10] and presents an alternative treatment option for tumors resistant to chemo-and/or radio-therapy [11,12]. For the treatment of microbes, PDT is also effective for some localized microbial infections, such as oral candidosis, periodontitis or chronic wounds [13,14], but its usefulness is not yet fully established.…”