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- Title
Assessment of 5-fluorouracil and 4-nitroquinoline-1-oxide in vivo genotoxicity with P ig-a mutation and micronucleus endpoints.
- Authors
Zhou, Changhui; Zhang, Min; Huang, Pengcheng; Tu, Honggang; Wang, Zheng; Dertinger, Stephen D.; Torous, Dorothea K.; Chang, Yan
- Abstract
Genotoxicity assessments were conducted on male Sprague Dawley rats treated with 5-fluorouracil (5-FU) and 4-nitroquinoline-1-oxide (4NQO) as part of an international validation trial of the Pig-a mutant phenotype assay. Rats were orally exposed to 0, 11.5, 23, or 46 mg/kg/day 5-FU for three consecutive days (Days 1-3); blood was sampled on Days −1, 4, 15, 29, and 45. Pig-a mutant phenotype reticulocyte (RETCD59−) and mutant phenotype erythrocyte (RBCCD59−) frequencies were determined on Days −1, 15, 29, and 45, and percent micronucleated reticulocytes (%MN-RET) were measured on Day 4. Rats were treated with 4NQO for 28 consecutive days by oral gavage, at doses of 1.5, 3, or 6 mg/kg/day. RBCCD59− and RETCD59− frequencies were determined on Days −1, 15, and 29, and MN-RET were quantified on Day 29. Whereas 5-FU was found to increase %MN-RET, no significant increases were observed for RBCCD59− or RETCD59− at any of the time points studied. The high dose of 4NQO (6 mg/kg/day) was observed to markedly increase RBCCD59− and RETCD59− frequencies, and this same dose level caused a weak but significantly elevated increase in MN-RET (approximately twofold). Collectively, the results provide additional support for the combination of Pig-a mutation and MN-RET into acute and 28-day repeat-dose studies. Environ. Mol. Mutagen. 55:735-740, 2014. © 2014 Wiley Periodicals, Inc.
- Subjects
FLUOROURACIL; NITROQUINOLINE oxide; NUCLEOLUS; GENETIC toxicology; RETICULOCYTES; ERYTHROCYTES
- Publication
Environmental & Molecular Mutagenesis, 2014, Vol 55, Issue 9, p735
- ISSN
0893-6692
- Publication type
Article
- DOI
10.1002/em.21893