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Effet de l'irradiance sur la déplétion photochimique en oxygène après photosensibilisation de sphéroïdes et de xénogreffes tumorales par la méta-tétra(hydroxyphénil)chlorine : activation par photosensibilisation de monocytes différenciés en macrophages

Abstract : Fluence rate effect was studied in multicell Colo26 mouse colorectal tumor spheroid and in mice bearing human colon adenocarcinoma HT29 tumors photosensitized by mTHPC (meta-tetra(hydroxyphenyl)chlorin), in arder to establish a direct relationship between light regimen, photodynamic therapy (PDT) efficacy and tumor oxygenation, and to evaluate the relative prevalence of the cytotoxic and vascular effects of PDT. The impact of photosensitization on the activity of immune cells was also evaluated. mTHPC photodegradation and PDT efficacy in Col026 spheroids lncreased when the fluence rate was progressively reduced from 90 to 5 mW/cm2. The consistence of these results with a mathematical model of photobleaching based on self-sensitized singlet oxygen C02) reactions with the photosensitizer ground state shows that the dependence on fluence rate is due to photochemical oxygen consumption and a predominantly 102-mediated mechanism of mTHPC photobleachlng. The threshold dose of reacting O2 is 7,9 ± 2,2 mM. Oxygen partial pressure (p02) of HT29 tumors irradiated at 160 or 90 mW/cm2 decreases significantly during irradiation, whereas tumor oxygenation is maintained in tumors treated at 30 or 5 mW/cm2. The return of the pO2 data 5 min after the end of PDT to values at least equal to baseline levels exclude the possibility of significant vessel damage during PDT. Tumors treated at 30 and 5 mW/cm2 exhibited longer tumor quadrupling time than tumors treated at 160 or 90 mW/cm2. These results are comparable to those obtained in spheroids, so direct photocytotoxic effects could be prevalent in our system. Sublethal doses of light lead to the activation of the phagocytic activity of U937 monocytes differenciated into macrophages, and of the production of tumar necrosis factor-a and nitric oxide. The activation of macrophages during mTHPC-based PDT could play a role in tumor destruction.
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http://docnum.univ-lorraine.fr/prive/SCD_T_2001_0273_COUTIER.pdf
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https://hal.univ-lorraine.fr/tel-01746474
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Submitted on : Thursday, March 29, 2018 - 10:38:33 AM
Last modification on : Thursday, October 22, 2020 - 3:39:04 PM

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Stéphanie Coutier. Effet de l'irradiance sur la déplétion photochimique en oxygène après photosensibilisation de sphéroïdes et de xénogreffes tumorales par la méta-tétra(hydroxyphénil)chlorine : activation par photosensibilisation de monocytes différenciés en macrophages. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2001. Français. ⟨NNT : 2001NAN11316⟩. ⟨tel-01746474⟩

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