Rodent fibroblast model for studies of response of malignant cells to exogenous 5-aminolevulinic acid.
All nucleated mammalian cells synthesize protoporphyrin IX (PpIX) when exposed to exogenous 5-aminolevulinic acid (ALA). The response to exogenous ALA under standard conditions (the ALA phenotype) is characteristic for each cell type. Significantly more PpIX accumulates in malignant and premalignant cells than in the normal cells from which they were derived. A rodent fibroblast model was developed to study the mechanisms responsible for this phenomenon. Exogenous ALA induced the accumulation of substantial concentrations of PpIX in fibrosarcoma cells, and in immortalized fibroblasts transfected 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 resistance selection. Much lower concentrations of PpIX accumulated in primary fibroblast 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 transformed cells (the malignant ALA phenotype) therefore appear to be closely linked to the mechanisms responsible for malignant transformation. Identification of the nature of that linkage may lead to new approaches to cancer therapy.
Li
G
G
Department of Microbiology and Immunology, Queen's University, Kingston, Ontario, Canada.
Szewczuk
M R
MR
Raptis
L
L
Johnson
J G
JG
Weagle
G E
GE
Pottier
R H
RH
Kennedy
J C
JC
D016475:3T3 Cells; D000622:Aminolevulinic Acid / Q000494:pharmacology*; D000818:Animals; D002461:Cell Line, Transformed; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002472:Cell Transformation, Viral; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D005354:Fibrosarcoma / Q000473:pathology; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000032:analysis; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009857:Oncogenes; D010641:Phenotype; D017319:Photosensitizing Agents / Q000494:pharmacology*; D011524:Protoporphyrins / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D011916:Rats, Inbred F344; D015398:Signal Transduction / Q000502:physiology; D013045:Species Specificity; D013050:Spectrometry, Fluorescence; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology
D005456:Fluorescent Dyes; D017319:Photosensitizing Agents; D011524:Protoporphyrins; D000622:Aminolevulinic Acid; C028025:protoporphyrin IX