Response to ALA-based PDT in an immortalised normal breast cell line and its counterpart transformed with the Ras oncogene.
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 photodynamic treatment in a tumour/normal cell line pair. We employed the HB4a cell line from normal mammary luminal epithelium and its counterpart transfected with the oncogen H-Ras (VAL/12 Ras). After 3 h of exposure to ALA, HB4a-Ras cells produce a maximum of 150 ng porphyrins per 10(5) cells whereas HB4a produce 95 ng porphyrins per 10(5) cells. In addition, HB4a-Ras cells show a plateau of porphyrin synthesis at 1 mM whereas HB4a porphyrins peak at the same concentration, and then decrease quickly. This higher porphyrin synthesis in the tumorigenic cell line does not lead to a higher response to the photodynamic treatment upon illumination. Lethal doses 50, LD(50), determined by MTT assay were 0.015 J cm(-2) and 0.039 J cm(-2) for HB4a and HB4a-Ras respectively after 3 h exposure to 1 mM ALA. The conclusion of this work is that a tumour cell line obtained by transfection of the Ras oncogene, although producing higher porphyrin synthesis from ALA, is more resistant to ALA-PDT than the parental non-tumour line, however the mechanism is not related to photosensitiser accumulation, but very likely to cell survival responses.
Centro de Investigaciones sobre Porfirinas y Porfirias (CIPYP), CONICET and Hospital de Clínicas José de San Martín, University of Buenos Aires, Viamonte 1881 10A, 1056 Buenos Aires, Argentina.
Lorena
L
Rodriguez
Gabriela
G
Divenosa
Alcira
A
Batlle
Alexander
A
Macrobert
Adriana
A
Casas
D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001940:Breast / Q000166:cytology; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005260:Female; D011905:Genes, ras / Q000235:genetics / Q000502:physiology*; D006801:Humans; D010778:Photochemotherapy; D011166:Porphyrins / Q000378:metabolism; D013997:Time Factors
D000970:Antineoplastic Agents; D011166:Porphyrins; D000622:Aminolevulinic Acid