title: Uptake of Lipiodol--cytotoxic conjugates by hepatoblastoma cells.
abstract: BACKGROUND
  Improvements in the management of children with hepatoblastoma have followed advances made in cytotoxic agents and treatment regimens. The aim of this study was to quantify the effect of Lipiodol, an iodinated poppy-seed oil, on the uptake of anthracyclic cytotoxic conjugates by hepatoblastoma cells in culture.
  
  
  METHODS
  Monolayer cultures of (1) a hepatoblastoma cell line generated from freshly explanted tumour tissue, (2) an immortal hepatoblastoma cell line (C3a) and (3) a human hepatocyte cell line were exposed to doxorubicin 10 microg/ml with or without 2 per cent Lipiodol for 1-72 h. The fluorescence intensity in the treated cells, which correlates with intracellular doxorubicin concentration, was measured by confocal laser scanning microscopy. Cytotoxicity was assessed by trypan blue exclusion and electron microscopy.
  
  
  RESULTS
  Doxorubicin accumulated in the nucleus and cytoplasm of all the cell lines. With Lipiodol, the mean fluorescence intensity of intracellular doxorubicin was increased for up to 48 h in both hepatoblastoma lines, but not in the hepatocyte cell line. Lipiodol increased the uptake and intracellular concentration of doxorubicin in the hepatoblastoma cells in culture. Lipiodol also enhanced the cytotoxicity of doxorubicin on the cultured hepatoblastoma cells.
  
  
  CONCLUSIONS
  Lipiodol significantly enhanced the uptake of doxorubicin by hepatoblastoma cells in culture. Lipiodol-doxorubicin targeted treatment of hepatoblastoma may improve the intracellular uptake and hence cytotoxicity of doxorubicin in vivo, enabling a reduction in the total dose administered and side-effects.
authors.affiliation: Department of Surgery, University College and Royal Free Medical School, Imperial College, London, UK. etowu@doctors.org.uk
authors.forename: E
authors.initials: E
authors.lastname: Towu
authors.forename: R
authors.initials: R
authors.lastname: Al-Mufti
authors.forename: L
authors.initials: L
authors.lastname: Spitz
authors.forename: K
authors.initials: K
authors.lastname: Marron
authors.forename: M
authors.initials: M
authors.lastname: Winslet
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002675:Child, Preschool; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D018197:Hepatoblastoma / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007459:Iodized Oil / Q000493:pharmacokinetics*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D018613:Microscopy, Confocal; D014407:Tumor Cells, Cultured
chemical_list: D000903:Antibiotics, Antineoplastic; D007459:Iodized Oil; D004317:Doxorubicin