EFFECT OF SOME ANTITUMOR DRUGS ON METABOLISM OF MOUSE LIVER CATALASE

抄録

The effect of five antitumor drugs on metabolism of mouse liver catalase was studied indirectly by determining catalase activity with a combined use of 3-amino-1, 2, 4-triazole. Kanamycin, Actinomycin-J, Mitomycin-C, 5-fluorouracil, and cycloheximide were intraperitoneally injected to mice (one-half of LD₅₀ dose/kg body weight/day, 4 times). Actinomycin-J, Mitomycin-C, and 5-fluorouracil produced greater decrease in liver catalase activity, and more retarded restoration of activity than Kanamycin and cycloheximide. When aminotriazole (1.0g/kg) was injected 24hr after the last (4th) drug injection to deplete catalase present in liver, retardation of the activity recovery was evidently observed when compared with the normal recovery curve following the aminotriazole injection. A similar tendency of inhibition of catalase biosynthesis by those antitumor drugs was demonstrated by plotting the difference in activity between aminotriazole-treated and antitumor drug plus aminotriazole-treated groups vs. time.
Daily injection of smaller amounts of the antitumor drugs (Kanamycin 0.5g, Actinomycin-J 0.04mg, Mitomycin-C 1.25mg, 5-fluorouracil 3.0mg, and cycloheximide 2.0mg/kg body weight) produced approximate plateaus during 5th to 8th day of injection. Under a similar condition, aminotriazole was injected (1.0g/kg) to estimate the rates of catalase synthesis (K_S) and degradation (K_D). K_D was greatly reduced by Mitomycin-C and cycloheximide, considerably by Actinomycin-J and 5-fluorouracil, and slightly by Kanamycin, whereas K_S was more strongly lowered by Actinomycin-J, Mitomycin-C, 5-fluorouracil, and cycloheximide than that by Kanamycin. It is suggested that the decrease in K_S by the antitumor drugs is responded by reduction of K_D for autoregulation of liver catalase metabolism.