Comparative studies were carried out on the possible parallelism between the effect of various anticancer agents and the restoration of the lowered activities of liver catalase and uricase to normal in mice bearing Ehrlich ascites carcinoma. Changes in liver xanthine oxidase activity during the therapy were also measured.
1) The alkylating agents used, which were active against Ehrlich ascites carcinoma, restored the lowered activities of catalase and uricase in tumor-bearing mice in parallel with their effect on the prolongation of the life span. However, they had no influence on the activity of these enzymes in normal mice.
2) Sarkomycin had the same effect as these alkylating agents.
3) Among the purine antagonists tested, 6-mercaptopurine and 8-azaguanine, which had considerable anticancer activity against Ehrlich ascites carcinoma, caused further reduction in the activities of catalase and uricase in tumor-bearers, and the restoration of these enzyme activities to normal was delayed. The non-effective purine antagonist, 2, 6-diaminopurine, had a tendency to depress the lowered enzyme activity in tumorbearers. All the purine antagonists tested inhibited xanthine oxidase activity in both normal and tumor-bearing mice.
4) Folic acid antagonists, which were not effective against Ehrlich ascites carcinoma at the dose level tested, further depressed the activities of catalase and uricase in tumor-bearing mice and subsequently did not restore the enzyme activity to normal. In normal mice, only catalase activity was inhibited, while xanthine oxidase activity was almost unaffected in both normal and tumor-bearing mice.
On the basis of these results, it is concluded that the effects of the anticancer agents tested in increasing the survival rate and in restoring the lowered activities of liver catalase and uricase in tumor-bearing mice were not always in parallel.
View full abstract