Modification of chemotherapeutic effects on L1210 cells using hematoporphyrin and light

Tissue culture experiments were done to evaluate the possibility of modifying the response curves of phenylalanine mustard (LPAM) and actinomycin D on L1210 cells, using moderately toxic levels of photodynamic injury provided by light and hematoporphyrin (HP). Cells were grown and treated in Roswell Park Memorial Institute Medium 1630 containing 20% horse serum. Cells were incubated with HP at concentrations of 1 to 50 microM for up to 48 hr. Illumination was provided by fluorescent light (4 milliwatts/sq cm), filtered through plastic to remove all wavelengths outside of the range of 400 to 800 nm. Ambient light was carefully controlled. When cells were incubated with 25 microM HP in the dark for 24 hr and then exposed to light for 1 hr, there were reductions in cloning efficiencies of 30 to 80% compared to the dark-HP-treated controls. When LPAM (1 to 30 microM) or actinomycin D (0.04 to 2.0 ng/ml) was incubated with cells for 1 hr following HP treatment, with or without light exposure, the LPAM response curves were modified to indicate a synergistic response of photodynamic toxicity and chemotherapeutic toxicity (one additional log). HP in the dark prior to and during LPAM exposure did not modify the LPAM response curve. The actinomycin D response curve was modified by prior HP and light treatment to indicate an additive effect of one additional log; a synergistic effect may be present in the range of 100 to 10% cloning efficiencies. It is concluded that the L1210-HP-light system offers possibilities for investigating the modification of chemotherapy effects.