Evaluation of Short-term Myelotoxicity Study in Dietary Reduced Rats |
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Authors: | Asanuma Fumiko Miyata Hiroto Iwaki Yoshinobu Kimura Masaaki Matsumoto Kiyoshi |
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Affiliation: | 1.Drug Safety and Pharmacokinetics Laboratories, Taisho Pharmaceutical Co., Ltd., 1–403 Yoshino-cho, Kita-ku, Saitama-shi, Saitama 331-9530, Japan;2.Division of Laboratory Animal Research, Department of Life Science, Research Center for Human and Environmental Sciences, Shinshu University, 3–1–1 Asahi, Matsumoto-shi, Nagano 390-8621, Japan |
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Abstract: | This study attempted to prove our hypothesis that a short-term toxicity study, using a 4-day dosing regimen as an example, is suitable for evaluating myelotoxicity in rats. We compared the hematological, bone marrow cytological and histopathological results of 5-fluorouracil (5-FU) treated and pair-feeding groups after a 4-day administration period. Several experimental groups were defined for this 4-day study as well as for our previously reported 14-day study (Miyata et al., 2009); these included 5-FU treated groups receiving 12, 15 and 18 mg/kg/day (FU12, FU15 and FU18), pair-feeding groups (R12, R15 and R18 receiving the same amount of food as the FU12, FU15 and FU18 groups, respectively) and a nontreated control group. Although severe reductions in body weight gain and food consumption were reported in the 14-day study, only slight reductions were observed in the 4-day study. In the 4-day study, a decrease in blood reticulocytes and a decreasing trend of marrow erythroid cells were only observed in the FU18 group, and no effects were observed in the pair-feeding groups. The erythroblastic changes observed in this 4-day study were thought to reflect the direct influence of 5-FU administration. Since concerns regarding the influence of secondary changes related to undernutrition were minimized in the 4-day study, it was thought to clarify the direct influence of 5-FU administration on erythroblastic cells. Thus, a 4-day study protocol might be helpful for distinguishing secondary changes related to undernutrition. |
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Keywords: | myelotoxicity short-term toxicity study dietary restriction 5-fluorouracil pair-feeding rat |
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