Influence of hepatic artery occlusion and desferrioxamine on liver-tumour growth.
The mechanisms behind tumour regression during ischaemic therapy of liver malignancy are not thoroughly elucidated. Ischaemia-reperfusion injury and release of free radicals is one mechanism suggested. The aim of the present study was to explore whether inhibition of hydroxyl radicals, by complex binding Fe with desferrioxamine (DFO), counteracted the retardation in tumour growth rate after HAL and whether DFO in itself had an effect on tumour growth in 2 experimental rat liver tumours. Rats with a hepatoma or an adenocarcinoma were subjected to HAL or to a sham procedure with or without additional injections of DFO daily for 2 or 7 days. HAL had an inhibitory effect on tumour growth rate. The effect of HAL was not counteracted by DFO, while DFO alone caused a decrease in tumour volume. There was an additive effect of DFO and HAL on tumour growth rate in both tumour systems. In vitro there was a growth inhibitory effect of DFO in both tumours, more pronounced in the hepatoma than in the adenocarcinoma. Our findings indicate that the effect of HAL is not mediated by release of oxygen free radicals. In the adenocarcinoma system, an additive effect of DFO and HAL was seen. As a rate-limiting enzyme for DNA synthesis is dependent on iron, depletion of iron can decrease mitotic activity, a mechanism that could explain the effect of DFO on tumour growth.
Lindnér
P
P
Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
Naredi
P
P
Peterson
A
A
Hafström
L
L
D000230:Adenocarcinoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003676:Deferoxamine / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D006499:Hepatic Artery; D017665:Hydroxyl Radical / Q000378:metabolism; D007501:Iron / Q000378:metabolism; D007502:Iron Chelating Agents / Q000378:metabolism / Q000494:pharmacology*; D007511:Ischemia / Q000378:metabolism; D008026:Ligation; D008099:Liver / Q000098:blood supply; D008114:Liver Neoplasms, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051381:Rats; D011920:Rats, Inbred WF
D007502:Iron Chelating Agents; D017665:Hydroxyl Radical; D007501:Iron; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D003676:Deferoxamine