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.