European Journal of Cancer
Volume 37, Issue 3 , Pages 414-421, February 2001

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

  • M.J. Jaroszeski

      Affiliations

    • Department of Surgery, MDC Box 16, College of Medicine, University of South Florida, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612-4799, USA
    • Center for Molecular Delivery, University of South Florida, Tampa, FL 33612-4799, USA
    • Corresponding Author InformationCorresponding author at first address. Tel.: +1-813-974-4662; fax: +1-813-974-2669
    • ,
  • D. Coppola

      Affiliations

    • G.I. Tumor Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
    • Department of Pathology, MDC11, College of Medicine, University of South Florida, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612-4799, USA
    • ,
  • G. Nesmith

      Affiliations

    • Department of Surgery, MDC Box 16, College of Medicine, University of South Florida, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612-4799, USA
    • ,
  • C. Pottinger

      Affiliations

    • Department of Surgery, MDC Box 16, College of Medicine, University of South Florida, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612-4799, USA
    • ,
  • M. Hyacinthe

      Affiliations

    • G.I. Tumor Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
    • ,
  • K. Benson

      Affiliations

    • Department of Pathology, MDC11, College of Medicine, University of South Florida, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612-4799, USA
    • ,
  • R. Gilbert

      Affiliations

    • Center for Molecular Delivery, University of South Florida, Tampa, FL 33612-4799, USA
    • Department of Chemical Engineering, ENB 118, College of Engineering, University of South Florida, 2202E Fowler Avenue, Tampa, FL 33620, USA
    • ,
  • R. Heller

      Affiliations

    • Department of Surgery, MDC Box 16, College of Medicine, University of South Florida, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612-4799, USA
    • Center for Molecular Delivery, University of South Florida, Tampa, FL 33612-4799, USA
    • Cutaneous Oncology Program, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA
    • Department of Medical Microbiology, University of South Florida, Tampa, FL 33612-4799, USA

Received 2 May 2000; received in revised form 29 September 2000; accepted 2 October 2000.

Abstract 

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.

Keywords:  Electrochemotherapy, Bleomycin, Electroporation, Electropermeabilisation, Liver

 

PII: S0959-8049(00)00407-X

European Journal of Cancer
Volume 37, Issue 3 , Pages 414-421, February 2001