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Genotoxic potency of three quinoline compounds evaluated in vivo in mouse marrow cells
1Medical and Health Sciences Division, Oak Ridge Associated Universities, Tennessee 37831-0117.
Abstract:
In vitro assays of the genotoxicity of quinoline compounds have yielded varying indications of their potency, and only limited determinations have been reported following in vivo administrations. We have quantified chromosome aberrations (CA) and sister chromatid exchanges (SCE) in the marrow cells of mice that had been injected with quinoline, 8-hydroxyquinoline, or 4-nitroquinoline-1-oxide up to levels approaching lethal. Treatments with quinoline produced no consistent increase in the number of aberrations at either 17 or 36 hr after treatment and no significant increase in SCE numbers at either 23 or 42 hr. Similarly, 8-hydroxyquinoline had no measurable effect on either CA or SCE but did tend to prolong the cell cycle. 4-Nitroquinoline-1-oxide was a very potent inducer of both CA and SCE as well as an inhibitor of cell division.
Insights
This study investigated the in vivo genotoxicity of quinoline compounds in mice. 4-Nitroquinoline-1-oxide strongly induced chromosome aberrations and sister chromatid exchanges, unlike quinoline or 8-hydroxyquinoline.
Area of Science:
- Toxicology
- Genetics
- Pharmacology
Background:
- In vitro studies show varying genotoxicity of quinoline compounds.
- Limited in vivo data exists for quinoline genotoxicity.
Purpose of the Study:
- To quantify in vivo genotoxicity of quinoline, 8-hydroxyquinoline, and 4-nitroquinoline-1-oxide.
- To assess chromosome aberrations (CA) and sister chromatid exchanges (SCE) in mouse marrow cells.
Main Methods:
- Mice were injected with quinoline, 8-hydroxyquinoline, or 4-nitroquinoline-1-oxide.
- Chromosome aberrations (CA) and sister chromatid exchanges (SCE) were quantified in bone marrow cells at various time points.
- Cell cycle progression was monitored.
Main Results:
- Quinoline and 8-hydroxyquinoline did not significantly increase CA or SCE.
- 8-Hydroxyquinoline showed a tendency to prolong the cell cycle.
- 4-Nitroquinoline-1-oxide was a potent inducer of CA and SCE and inhibited cell division.
Conclusions:
- 4-Nitroquinoline-1-oxide exhibits significant in vivo genotoxicity in mice.
- Quinoline and 8-hydroxyquinoline show minimal genotoxic effects in vivo under tested conditions.