PHOTODYNAMIC INACTIVATION OF R3230AC MAMMARY CARCINOMAIN VITROWITH HEMATOPORPHYRIN DERIVATIVE: EFFECTS OF DOSE, TIME, and SERUM ON UPTAKE and PHOTOTOXICITY

AbstractPrimary cultures of the R3230AC mammary adenocarcinoma were used for pharmacokinetic studies of hematoporphyrin derivative (HPD), a preparation containing several porphyrin species and useful as a photoactivatable anti‐tumor agent. Uptake of HPDin vitrowas shown to be time‐, dose‐ and temperature‐dependent with an apparent plateau reached at 2 ‐ 4 h. An increase in the amount of serum in the medium progressively reduced the amount of HPD taken up by the cells; at a level of 10% serum, uptake of HPD was reduced by >95%. The time‐course of efflux of HPD from these cells demonstrated a complex pattern, with an initial rapid component followed by a more gradual rate of efflux up to 4 h. Assessment of photoradiation‐induced cytotoxicity was performed by a method developed to quantitatively measure trypan blue exclusion. Relative cytotoxicity was determined by use of heat‐killed cells as a standard. At two different concentrations of HPD, cytotoxicity was dependent on light exposure time. The presence of serum, which reduced uptake of HPD was correctable to reduced cytotoxicity. Based on the amount of light exposure to produce 50% cell kill, an order of potency was obtained for HPD > hematoporphyrin > hydroxyethylvinyldeuteroporphyrinin vitro.This order of potency correlated with the relative proportion of hydrophobic components as estimated by HPLC analysis. The results indicate that HPD is an effective cytotoxic agentin vitroin a well‐differentiated mammary adenocarcinoma model.