Micronucleus assays on 5-fluorouracil and 6-mercaptopurine with mouse peripheral blood reticulocytes.
As part of the 5th collaborative study of the Collaborative Study Group for the Micronucleus Test (CSGMT), the sensitivity and advantages of the micronucleus assay using mouse peripheral blood cells were evaluated using 5-fluorouracil (5-FU) and 6-mercaptopurine (6-MP). The peripheral blood cells were collected from a tail vein of CD-1 male mice just before and 24-120 h after intraperitoneal injection. At 24-h intervals. The maximum incidence of micronucleated reticulocytes (MNRETs) at 50 mg/kg 5-FU was observed 96 h after injection; at 100 mg/kg, the peak was delayed to 120 h, and followed severe bone marrow depression. With 6-MP, maximum MNRETs were observed 48 h after treatment at all doses tested. At dose levels higher than 50 mg/kg, severe bone marrow depression was observed after maximum MNRETs. Though the appearance patterns of MNRETs and the bone marrow depression were different between 5-FU and 6-MP, the positive response of both chemical could be detected with this assay system as well as with the micronucleus test using femoral bone marrow cells.
Taiho Pharmaceutical Co. Ltd., Drug Safety Laboratory, Tokushima, Japan.
A
A
Ohuchida
A
A
Furukawa
J
J
Yoshida
M
M
Watanabe
F
F
Aruga
Y
Y
Miwa
K
K
Shinkawa
N
N
Kinae
D000818:Animals; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil / Q000633:toxicity*; D008297:Male; D015122:Mercaptopurine / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D015162:Micronucleus Tests / Q000379:methods; D016685:Mitomycin / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*; D012156:Reticulocytes / Q000187:drug effects*
D009153:Mutagens; D016685:Mitomycin; D015122:Mercaptopurine; D005472:Fluorouracil