Rodent fibroblast model for studies of response of malignant cells to exogenous 5-aminolevulinic acid

All nucleated mammalian cells synthesize protoporphyrin IX (PpIX) when expo sed to exogenous 5-aminolevulinic acid (ALA), The response to exogenous ALA under standard conditions (the ALA phenotype) is characteristic for each c ell type. Significantly more PpIX accumulates in malignant and premalignant cells than in the normal cells from which they were derived. A rodent fibr oblast model was developed to study the mechanisms responsible for this phe nomenon. Exogenous ALA induced the accumulation of substantial concentratio ns of PpIX in fibrosarcoma cells, and in immortalized fibroblasts transfect ed with the oncogene c-myc, IGF-1 receptor, IGF-1 and its receptor, v-fos, v-raf, v-Ki-ras, v-abl, or polyomavirus middle T antigen with G418 resistan ce selection. Much lower concentrations of PpIX accumulated in primary fibr oblast cultures, in immortalized fibroblast cell lines, and in immortalized fibroblasts transfected with the G418-resistance gene only. The mechanisms responsible for the increased accumulation of ALA-induced PpIX by transfor med cells (the malignant ALA phenotype) therefore appear to be closely link ed to the mechanisms responsible for malignant transformation. identificati on of the nature of that linkage may lead to new approaches to cancer thera py.