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[Mutagenicity studies of prednisolone farnesylate (PNF)]
M Otsuka1, S Ajimi, Y Kajiwara
1Hita Research Laboratories, Chemicals Inspection and Testing Institute 3-822, Oita, Japan.
Abstract:
Prednisolone farnesylate (PNF) was tested for mutagenicity by Ames test using Salmonella typhimurium (TA100, TA1535, TA98, TA1537) and Escherichia coli (WP2 uvrA), for clastogenic activity in vitro by the chromosomal aberration test in a Chinese hamster fibroblast cell line (CHL), and for induction of micronuclei by the micronucleus test in male ICR mice. 1) In Ames test, PNF with and without metabolic activation showed no mutagenicity in any strains at any dose levels (312-5,000 micrograms/plate). 2) In the chromosomal aberration test, PNF with metabolic activation produced a slight increase in the incidence of structural chromosomal aberrations in CHL cells at 1,500 micrograms/ml. 3) In the micronucleus test, a single administration of PNF caused no significant increase of micronucleated polychromatic erythrocytes at any doses (250-2,000 mg/kg).
Insights
Prednisolone farnesylate (PNF) demonstrated no mutagenicity in bacterial assays. While a slight increase in chromosomal aberrations was observed in vitro, PNF did not induce micronuclei in vivo, suggesting a low genotoxic risk.
Area of Science:
- Toxicology
- Genotoxicity Testing
- Pharmacology
Background:
- Prednisolone farnesylate (PNF) is a corticosteroid derivative.
- Assessing the genotoxic potential of pharmaceutical compounds is crucial for safety evaluation.
Purpose of the Study:
- To evaluate the mutagenicity, clastogenicity, and in vivo genotoxicity of Prednisolone farnesylate (PNF).
- To determine the safety profile of PNF regarding genetic damage.
Main Methods:
- Bacterial Reverse Mutation Assay (Ames test) using Salmonella typhimurium and Escherichia coli.
- In vitro chromosomal aberration test in Chinese hamster fibroblast cells (CHL).
- In vivo micronucleus test in male ICR mice.
Main Results:
- PNF showed no mutagenic activity in the Ames test across all bacterial strains, with or without metabolic activation.
- A slight increase in structural chromosomal aberrations was observed in CHL cells with metabolic activation at 1,500 µg/ml.
- PNF did not induce a significant increase in micronuclei formation in mouse bone marrow cells.
Conclusions:
- Prednisolone farnesylate exhibits no mutagenic potential in bacterial systems.
- The in vitro clastogenic effect observed at high concentrations requires careful consideration but was not replicated in vivo.
- PNF demonstrated a lack of in vivo genotoxicity in the micronucleus test, supporting its safety profile.