IMPROVED PHOTOCHEMOTHERAPY OF MALIGNANT-CELLS WITH DAUNOMYCIN AND THEKTP LASER

Laser photochemotherapy of malignancies may become an effective pallia tive treatment for advanced had and neck cancer using light-sensitive, chemotherapeutic drugs activated in tumors via interstitial laser fib eroptics. Previously, it was reported that cultured human P3 squamous cells incubated 2 hours with daunomycin (Dn) exhibited tenfold enhance d cytotoxicity after exposure to argon laser light at 514 nm. This sho rtterm uptake leads to drug localization in cytoplasmic and membrane s ites prior to nuclear accumulation and daunomycin topoisomerase inhibi tion. In the current study phototoxicity of Dn-sensitized human cancer cells was tested using broad-spectrum white light compared to monochr omatic green-wavelength light. Drug uptake and laser energy levels wer e optimized for maximum synergy. To test light-enhanced chemotherapy i n vitro, the kinetics of cell uptake and toxicity of daunomycin was me asured at 1, 2, and 5 mu g/ml in three human tumor cell lines: P3 squa mous-cell carcinoma, M26 melanoma, and TE671 fibrosarcoma. After 2 hr Dn uptake, all cell lines were tested for phototherapy response by exp osure to 300- to 900-nm visible light from a xenon lamp or monochromat ic 532-nm green light from a RTTP laser. When the KTP laser output was varied from 0 to 120 Joules in Dn-sensitized tumor cells, a linear ph ototherapy response was seen with energy as low as 12 J inducing drug phototoxicity. These results provide evidence that daunomycin cytotoxi city is enhanced when exposed to 532-nm laser illumination in the thre e tumor types tested and confirm that the response is related to both energy level and drug dose. Lasers Surg. Med. 23:33-39, 1998. (C) 1998 Wiley-Liss, Inc.