Effects of electrochemotherapy with bleomycin on normal liver tissue in a rat model

Preliminary studies that used electric pulses in vivo to facilitate entry of chemotherapeutic agents into tumour cells resulted in a 69% complete response rate for hepatocellular carcinoma in rats. This success motivated a focused investigation to define the adverse effects of this treatment on normal liver tissue. Bleomycin doses ranging from 0.5 to 2.5 U and electric fields from 500 to 2250 V/cm were investigated. Electrical treatment was administered using an array of six needles arranged in a circular pattern. Necrosis and four other histological parameters were examined 14 and 56 days after treatment. Results indicated that treatment effects were localised to the volume of treated tissue. These parameters, at both time points, were not significantly altered for liver tissue that was treated with all drug doses and electric fields of 1250 V/cm and below. Only the combination of more intense electric pulses with bleomycin produced adverse histological events in the form of localised liver necrosis at day 14. These effects were not visible at day 56. Liver function was normal through all of the treatment except for an elevation of several enzymes 1 day post-treatment.