Response to ALA-based PDT in a normal breast cell line and its transformed with the Ras oncogene

RODRÍGUEZ, LORENA; DI VENOSA, GABRIELA; BATLLE ALCIRA; MACROBERT, ALEXANDER; CASAS, ADRIANA

Shangai, China

Congreso; 11th World Congress of the International Photodynamic Association - IPA 2007; 2007

International Photodynamic Association

Introduction: Aminolevulinic acid (ALA)-based photodynamic therapy (PDT) has been successfully employed in the treatment of certain tumours. Porphyrins endogenously generated from ALA induce tumour regression after illumination with light of an appropriate wavelength. The aim of this work was to compare porphyrin production from ALA and sensitivity to PDT in a tumour/normal cell line pair.  Material & methods: We employed the HB4a cell line from normal mammary luminal epithelium and its derived transfected with the oncogen H-Ras (VAL/12 Ras). Results: After 3 hs of exposure to ALA, HB4a cells produce a maximum of 170 ng porphyrins/105 cells whereas HB4a-Ras produce 95 ng porphyrins/105 cells.  In addition, HB4a shows a plateau of porphyrin synthesis at 1 mM whereas HB4a-Ras porphyrins peak at the same concentration, and then decrease quickly probably due to dark toxicity induced by ALA. This lower porphyrin synthesis in the tumorigenic cell line leads to a lower response to PDT upon illumination with a bank of  fluorescent tubes. Lethal doses 50 were 0.014 J/cm2 and 0.034 J/cm2 for HB4a and HB4a-Ras respectively after 3 h exposure to 2 mm ALA.  Conclusions: A tumor cell line obtained by transfection of the Ras oncogene is more resistant to ALA-PDT than the parental non-tumor line.