2003 Volume 19 Issue 1 Pages 23-30
We have demonstrated that free radical reactions play an important role in the mechanism of the antitumor effect of hyperthermia (HT). In an attempt to enhance its antitumor effect, we studied the influence of the depletion of glutathione (GSH), a typical radical scavenger in AH 109A carcinoma, a rat liver cancer. Oral administration of buthionine sulphoximine (BSO), a GSH synthesis inhibitor, caused a decrease in the tumor GSH content and enhanced the effect of HT. However, oral administration has the potential to cause adverse effects because it also decreases GSH in other tissues. To avoid this problem, we injected BSO into the feeding artery for the tumor, and examined the changes of the GSH content in the tumor, liver, and kidneys. It was found that the GSH content of the liver and kidneys decreased soon after the injection of BSO and recovered completely after 24 h, while the decrease of GSH in the tumor persisted. When HT was done at this time, it showed an enhanced antitumor effect.
The above results suggest that the intraarterial injection of BSO can specifically decrease the tumor GSH content, and can enhance the antitumor effect of HT without having an adverse effect on normal organs.