ANTITUMOR AGENTS. I. EFFECT OF 5-FLUOROURACIL AND CYCLOPHOSPHAMIDE ON LIVER MICROSOMES AND THYMUS OF RAT

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Effects of antitumor agents on rat liver microsomal drug-metabolizing enzyme activities and thymus lymphocytes were studied in male Wistar rats. High doses of 5-fluorouracil (5-FU) and cyclophosphamide (CP) given parenterally for 6 days caused a partial decrease in whole body weight and the microsomal enzyme content such as cytochrome P-450 and cytochrome b<SUB>5</SUB>. Aniline p-hydroxylase and aminopyrine N-demethylase activities also decreased in rats given CP for 6 days. The Michaelis constant for aniline p-hydroxylase of rats dosed for 5 days decreased compared with the control. Both compounds in the high concentrations produced spectral change of “modified type II”. However, the magnitude of the spectral changes observed was independent of the concentration of substrate added. The addition of NADPH to the microsomes-substrate mixture modified the spectral change. Both drugs caused a considerable decrease in thymus weight and the number of thymus lymphocytes, while the alkaline phosphatase activity was enhanced in 5-FU group, indicating that the agents cause a significant involution of the thymus. Decrease in the total number of the lymphocytes was greater than that in the blood leucocytes.
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