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[Immunotoxic effects of a new antineoplastic agent S-1 in mice--comparison with S-1, UFT and 5-FU]
Y Kouchi1, Y Maeda, H Morinaga
1Drug Safety Research Laboratory, Taiho Pharmaceutical Co., Ltd., Tokushima, Japan.
Abstract:
The immunotoxicity of S-1, which is a new antineoplastic agent, was investigated in BALB/c mice. S-1 contains tegafur (FT), CDHP, and potassium oxonate (Oxo) in a molecular ratio of 1:0.4:1. 5-fluorouracil (5-FU) and UFT were used as reference drugs. S-1 and reference drugs were administered by oral gavage for 7 days. The high dose employed in this study was determined as the maximally tolerated dose of a 9-day repeated-dose study in sarcoma 180-bearing mice. Decreased body weight was observed in mice treated with 5-FU and UFT but not in those treated with S-1. A significant decrease in thymus and spleen weight was observed in S-1-, UFT- and 5-FU-treated mice, and the degree was same for the three drugs. Though the number of white blood cells decreased dose-dependently for the three drugs, S-1 had the weakest effect. The number of red blood cells also decreased, but the effect was not dose-dependent, and its magnitude was the same for the 3 drugs. S-1 induced a dose-dependent decrease in the IgM antibody PFC response to sheep erythrocytes. The delayed type hypersensitivity response used a footpad reaction method was significantly suppressed at the highest dose of S-1. 5-FU and UFT suppressed humoral and cell-mediated immunity in almost the same manner as S-1. The degree of suppressive effects was greater on the humoral immune response than on the cell-mediated immune response. The number of CFU-GM colonies was significantly decreased in the highest dose group of each drug and in a lower group as well in S-1-treated mice. This finding might reflect the fact that S-1 induced continuous high levels of 5-FU in the blood. Under these experimental conditions, S-1 induced immunosuppressive effects in BALB/c mice, and the degree of suppression was almost same as that induced by 5-FU and UFT.
Insights
S-1, an antineoplastic agent, demonstrated immunosuppressive effects in mice, similar to 5-fluorouracil (5-FU) and UFT. While S-1 did not decrease body weight, it significantly reduced thymus and spleen weights, impacting immune responses.
Area of Science:
- Immunology
- Pharmacology
- Oncology
Background:
- S-1 is a novel oral antineoplastic agent containing tegafur (FT), CDHP, and potassium oxonate (Oxo).
- Understanding the immunotoxicity of S-1 is crucial for its clinical application.
- 5-fluorouracil (5-FU) and UFT serve as relevant comparators for evaluating S-1's effects.
Purpose of the Study:
- To investigate the immunotoxicity of S-1 in a murine model.
- To compare the immunosuppressive effects of S-1 with 5-FU and UFT.
- To assess the impact of S-1 on humoral and cell-mediated immunity.
Main Methods:
- BALB/c mice were administered S-1, 5-FU, or UFT via oral gavage for 7 days.
- Organ weights (thymus, spleen), blood cell counts (WBC, RBC), and antibody production (IgM PFC) were measured.
- Delayed type hypersensitivity (DTH) response and CFU-GM colony formation were assessed.
Main Results:
- S-1 treatment did not decrease body weight, unlike 5-FU and UFT.
- Significant reductions in thymus and spleen weights were observed for all three drugs.
- S-1 exhibited a dose-dependent decrease in IgM PFC response and DTH, with comparable or weaker effects than 5-FU and UFT on immune cell counts.
Conclusions:
- S-1 induces immunosuppressive effects in mice, comparable to 5-FU and UFT.
- The immunotoxicity of S-1 involves suppression of both humoral and cell-mediated immunity.
- S-1's impact on immune parameters warrants consideration in its therapeutic use.