ALA-PDT SENSITIVITY OF CELL LINES RESISTANT TO NITRIC OXIDE CYTOTOXICITY

Gabriela Divenosa, Adriana Casas, Christian Perotti, Haydee Fukuda & Alcira Batlle

Centro de Investigaciones dsbre Porfirinas y Porfirias (CIPYP), CONICET and University of Buenos Aires

In an attempt to elucidate interactions between aminolevulinic acid-based photodynamic therapy (ALA-PDT) and nitric oxide (NO) cytotoxicity, we employed a murine mammary adenocarcinoma cell line LM3 and the NO resistant variant LM3-SNP.

LM3 –SNP cells were more sensitive to ALA-PDT treatment, and by multiple exposures to ALA-PDT treatment, two cell lines resistant to ALA-PDT identified as Clon 1 and Clon 3 were isolated, which were 9.2 and 12.5 times more resistant to the  photosensitizing treatment than the parental cells.

In addition, the degree of resistance to the NO donor sodium nitroprussiate (SNP) was similar to that obtained for the parental LM3 line, and they did not show modifications in NO production, although the sensitivity to NO decreased in Clon 1 and increased in Clon3.

These results are indicating that resistance to ALA-PDT is not correlated with different degrees of resistance to NO toxicity, suggesting that NO resistance and ALA-PDT resistance are controlled by  independent pathways.