-transparent.png){kind=logo}
Photodynamic therapy (PDT) with Photofrin has already been authorized for certain applications in Japan, the USA and France, and powerful second-generation sensitizers such as meta-(tetrahydroxyphenyl) chlorin (m-THPC) are now being considered for approval. Although sensitizers are likely to localize within the cytoplasm or the plasma membrane, nuclear membrane can be damaged at an early stage of photodynamic reaction, resulting in DNA lesions. Thus, it is of critical importance to assess the safety of m-THPC-PDT, which would be used mainly against early well-differentiated cancers. In this context, m-THPC toxicity and phototoxicity were studied by a colorimetric MTT assay on C6 cells to determine the LD50 (2.5 microg/ml m-THPC for 10 J/cm2 irradiation and 1 microg/ml for 25 J/cm2 irradiation) and PDT doses inducing around 25% cell death. Single-cell electrophoresis (a Comet assay with Tail Moment calculation) was used to evaluate DNA damage and repair in murine glioblastoma C6 cells after LD25 or higher doses for assays of PDT. These results were correlated with m-THPC nuclear distribution by confocal microspectrofluorimetry. m-THPC failed to induce significant changes in the Tail Moment of C6 cells in the absence of light, whereas m-THPC-PDT induced DNA damage immediately after irradiation. The Tail Moment increase was not linear (curve slope being 43 for 0-1 microg/ml m-THPC and 117 for 1-3 microg/ml), but the mean value increased with the light dose (0, 10 or 25 J/cm2) and incubation time (every hour from 1 to 4 h) for an incubation with m-THPC 1 microg/ml. However, cultured murine glioblastoma cells were capable of significant DNA repair after 4 h, and no residual DNA damage was evident after 24-h post-treatment incubation at 37 degrees C. An increase in the light dose appeared to be less genotoxic than an increase in the m-THPC dose for similar toxicities. Our results indicate that m-THPC PDT appears to be a safe treatment since DNA repair seemed to not be impaired and DNA damage occurred only with lethal PDT doses. However, the Comet assay cannot give us the certainty that no mutation, photoadducts or oxidative damage have been developed so this point would be verified with another mutagenicity assay.
N Rousset, and
E Keminon, and
S Eléouet, and
T Le Néel, and
J L Auget, and
V Vonarx, and
J Carré, and
Y Lajat, and
T Patrice
January 2024,
Methods in molecular biology (Clifton, N.J.),
N Rousset, and
E Keminon, and
S Eléouet, and
T Le Néel, and
J L Auget, and
V Vonarx, and
J Carré, and
Y Lajat, and
T Patrice
January 2023,
Methods in molecular biology (Clifton, N.J.),
N Rousset, and
E Keminon, and
S Eléouet, and
T Le Néel, and
J L Auget, and
V Vonarx, and
J Carré, and
Y Lajat, and
T Patrice
June 2002,
Apoptosis : an international journal on programmed cell death,
N Rousset, and
E Keminon, and
S Eléouet, and
T Le Néel, and
J L Auget, and
V Vonarx, and
J Carré, and
Y Lajat, and
T Patrice
December 2020,
Nature protocols,
N Rousset, and
E Keminon, and
S Eléouet, and
T Le Néel, and
J L Auget, and
V Vonarx, and
J Carré, and
Y Lajat, and
T Patrice
January 2008,
Radiation research,
N Rousset, and
E Keminon, and
S Eléouet, and
T Le Néel, and
J L Auget, and
V Vonarx, and
J Carré, and
Y Lajat, and
T Patrice
January 2014,
Frontiers in genetics,
N Rousset, and
E Keminon, and
S Eléouet, and
T Le Néel, and
J L Auget, and
V Vonarx, and
J Carré, and
Y Lajat, and
T Patrice
March 1996,
International journal of radiation biology,
N Rousset, and
E Keminon, and
S Eléouet, and
T Le Néel, and
J L Auget, and
V Vonarx, and
J Carré, and
Y Lajat, and
T Patrice
November 2009,
Lasers in surgery and medicine,
N Rousset, and
E Keminon, and
S Eléouet, and
T Le Néel, and
J L Auget, and
V Vonarx, and
J Carré, and
Y Lajat, and
T Patrice
June 2000,
Journal of occupational and environmental medicine,
N Rousset, and
E Keminon, and
S Eléouet, and
T Le Néel, and
J L Auget, and
V Vonarx, and
J Carré, and
Y Lajat, and
T Patrice
August 1999,
Journal of occupational and environmental medicine,
