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

Preliminary studies that used electric pulses in vivo to facilitate entry o f chemotherapeutic agents into tumour cells resulted in a 69% complete resp onse rate for hepatocellular carcinoma in rats. This success motivated a fo cused investigation to define the adverse effects of this treatment on norm al liver tissue. Bleomycin doses ranging fi om 0.5 to 2.5 U and electric fi elds from 500 to 2250 V/cm were investigated. Electrical treatment was admi nistered using an army of six needles arranged in a circular pattern. Necro sis and four other histological parameters were examined 14 and 56 days aft er treatment. Results indicated that treatment effects were localised to th e volume of treated tissue. These parameters. at both time points, were not significantly altered for liver tissue that was treated with all drug dose s 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 e xcept for an elevation of several enzymes 1 day posttreatment. (C) 2001 Els evier Science Ltd. All rights reserved.