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Integration of micronucleus tests with a gene mutation assay in F344 gpt delta transgenic rats using benzo[a]pyrene.
- Source :
-
Mutation research. Genetic toxicology and environmental mutagenesis [Mutat Res Genet Toxicol Environ Mutagen] 2019 Jan; Vol. 837, pp. 1-7. Date of Electronic Publication: 2018 Sep 16. - Publication Year :
- 2019
-
Abstract
- Reduction of the number of animals used in in vivo genotoxicity tests is encouraged. For this purpose, we conducted integrated toxicity tests combining gene mutation assays with multiple-organ micronucleus (MN) tests (peripheral blood, bone marrow, liver, and colon) in F344 gpt delta transgenic (Tg) rats. Seven-week-old male F344 gpt delta rats were orally administered 62.5 or 125 mg/kg/day benzo[a]pyrene (B[a]P) for 28 days. One day after the final day of treatment (day 29) and three days after the final treatment (day 31), bone marrow, liver, and colon samples were collected, and mutation assays and MN tests were performed. The gpt mutant frequency (MF) significantly increased in bone marrow, liver and colon but MN induction was only significant in bone marrow but not in liver and colon. Similarly MN induction was only observed in bone marrow in non-Tg F344 rats. In peripheral blood obtained on day 4, 15, 29, 31, a time-dependent increase was observed in reticulocyte MN frequency during the treatment. Thus, our integrated method successfully detected both gene mutations and MN induction caused by B[a]P. In addition, no significant differences were observed between sampling times (day 29 versus 31), suggesting that sampling on day 29 is also valid to evaluate gene mutations. On the other hand, MN results in bone marrow and peripheral blood were different depending on the sampling day. An appropriate sampling day should be designated according to which assays are integrated. We confirmed that integration of the MN test with a gene mutation assay using F344 gpt delta Tg rats is useful to evaluate different endpoints related to genotoxicity using the same animals and to reduce animal use.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- Animals
Bone Marrow drug effects
Colon drug effects
Liver drug effects
Male
Rats
Rats, Inbred F344
Rats, Transgenic
Reticulocytes drug effects
Benzo(a)pyrene pharmacology
Carcinogens pharmacology
Micronuclei, Chromosome-Defective chemically induced
Micronucleus Tests methods
Mutagenicity Tests methods
Mutagens pharmacology
Transferases (Other Substituted Phosphate Groups) genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3592
- Volume :
- 837
- Database :
- MEDLINE
- Journal :
- Mutation research. Genetic toxicology and environmental mutagenesis
- Publication Type :
- Academic Journal
- Accession number :
- 30595204
- Full Text :
- https://doi.org/10.1016/j.mrgentox.2018.09.003