Photodynamic therapy of activated and resting lymphocytes and its antioxidant adaptive response.
In this work we have studied the effects of ALA-mediated photodynamic therapy (PDT) on resting and mitogen-activated murine splenic lymphocytes, evaluating its impact on cell viability. We have also characterised the stress response, measuring the levels of antioxidant enzymes. A 2h exposure to ALA produced 50% lethality upon irradiation of activated cells with 2.1J/cm2. The decrease in cell survival with increasing time exposure to ALA, correlated well with the higher porphyrin accumulation. In resting lymphocytes, in spite of the low amount of porphyrins formed during 2h incubation with ALA, 40% of the cells died after irradiation, this response was not further increased when higher amounts of porphyrins were synthesised. Superoxide dismutase was impaired by light treatment independently of ALA exposure in activated lymphocytes and, to a lesser extent, in resting lymphocytes. PDT induced an antioxidant adaptive response in activated cells 19 h after irradiation, reflected as a net increase in GSHPx activity and a slight reversion of the catalase (CAT) activity already impaired by light treatment. PDT treatment of activated cells also produced a diminution in the GSH/GSSG ratio. Only activated cells are capable of developing an antioxidant adaptive response to PDT treatment.
Casas
A
A
Centro de Investigaciones sobre Porfirinas y Porfirias FCEyN, University of Buenos Aires, Argentina.
Perotti
C
C
Fukuda
H
H
del C  Batlle
A M
AM
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002470:Cell Survival; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011166:Porphyrins / Q000096:biosynthesis; D011506:Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000975:Antioxidants; D017319:Photosensitizing Agents; D011166:Porphyrins; D011506:Proteins; D000622:Aminolevulinic Acid; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione