Effect of mammalian cell differentiation on response to exogenous 5-aminolevulinic acid

Many different types of mammalian cells accumulate fluorescing and photosen sitizing concentrations of protoporphyrin IX (PpIX) when exposed to exogeno us 5-aminolevulinic acid (ALA) in vivo or in vitro. Most types of malignant cells accumulate substantially more ALA-induced PpIX than do the normal ce lls from which they arose. Most types of malignant cells also are less diff erentiated than their normal counterparts. We therefore considered the poss ibility that malignant cells demonstrate a malignant ALA phenotype (accumul ate abnormally large amounts of PpIX when exposed to exogenous ALA) as a di rect consequence of their less differentiated state, Human promyelocyte cel l lille HL-60 and mouse preadipocyte cell line 3T3 L1 were induced to diffe rentiate by exposing them to inducing agents in vitro, The HL-60 cells accu mulated less ALA-induced PpIX when differentiated, but the 3T3 L1 cells acc umulated more. It appears then that changes in the ALA phenotype with chang es in the state of differentiation are cell type specific. The decreased ac cumulation of ALA-induced PpIX that accompanied differentiation of the prom yelocytic leukemia cells may have clinical application for rapid quantitati on of the response of myelocytic leukemia patients to differentiation thera py.