Fetal liver micronucleus assay in mice of 5-fluorouracil and related compounds.
The cytogenetic effects of 5-fluorouracil (5-FU), 1-hexyl-carbamoyl-5- fluorouracil (HCFU) and 1-(2-tetrahydrofuryl)-5-fluorouracil (TF) were examined with the fetal liver micronucleus assay in mice. The frequencies of micronucleated polychromatic erythrocytes (MNPCEs) in fetal liver peaked at 27, 24 and 27 h, respectively, after single intraperitoneal injections into pregnant mice on day 13 of gestation. The highest frequency of MNPCEs by 5-FU treatment in fetal liver was 13.6%, whereas the frequency in maternal bone marrow was only 0.4%. The micronucleus frequency and the number of micronuclei per individual polychromatic erythrocyte were clearly dose-dependent. These results suggest that the micronucleus test in fetal liver has particular advantages compared to maternal bone marrow for evaluating the cytogenetic effects of 5-FU and related compounds after a single treatment. The cytogenetic effect was ranked 5-FU = HCFU > TF, in both a time-course study and a dose-response study of micronucleus distribution.
Nakamura
M
M
Drug Safety Research Laboratory, Takeda Chemical Industries Ltd., Osaka, Japan.
Fort
F L
FL
Kikuchi
Y
Y
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005333:Fetus / Q000187:drug effects; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000633:toxicity*; D008099:Liver / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D015162:Micronucleus Tests; D005641:Tegafur / Q000633:toxicity*
D005641:Tegafur; C017367:carmofur; D005472:Fluorouracil