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Micronucleus test with benzo[a]pyrene using a single peroral administration and intraperitoneal injection in males of
Abstract:
The effect of route of administration on the outcome of the micronucleus test was examined by administering benzo[a]pyrene (B[a]P) perorally (p.o.) and intraperitoneally (i.p.) to males of the MS/Ae and CD-1 mouse strains. This study consisted of 3 parts. First, an acute toxicity study lasting 3 days was done to estimate LD50s. The LD50 was larger than 1600 mg/kg for both routes in the 2 strains. Second, pilot micronucleus tests were carried out, on the basis of which an appropriate sampling time (48 h) and dose levels (62.5, 125, 250, and 500 mg/kg) were chosen for both routes and both strains. Third, full-scale micronucleus tests were done, which indicated that (1) B[a]P induced micronuclei dose-dependently by each administration route in each strain, (2) the i.p. route induced frequencies of micronuclei almost equal to or slightly higher than did the p.o. route, and (3) the MS/Ae strain was the higher responder.
Insights
Benzo[a]pyrene (B[a]P) administration route impacts micronucleus test outcomes. Intraperitoneal (i.p.) and peroral (p.o.) routes showed similar genotoxicity, with the MS/Ae mouse strain being more sensitive.
Area of Science:
- Toxicology
- Genetics
- Pharmacology
Background:
- The micronucleus test is a standard genotoxicity assay.
- Understanding administration route effects is crucial for accurate toxicity testing.
Purpose of the Study:
- To evaluate how the route of administration (peroral vs. intraperitoneal) affects benzo[a]pyrene (B[a]P) genotoxicity in the micronucleus test.
- To compare the responsiveness of MS/Ae and CD-1 mouse strains to B[a]P exposure.
Main Methods:
- Acute toxicity studies to determine LD50 values for both administration routes.
- Pilot micronucleus tests to establish optimal sampling times and dose levels.
- Full-scale micronucleus tests using B[a]P at doses of 62.5, 125, 250, and 500 mg/kg.
Main Results:
- Benzo[a]pyrene induced micronuclei in a dose-dependent manner via both peroral and intraperitoneal routes.
- Intraperitoneal administration resulted in micronucleus frequencies comparable to or slightly higher than peroral administration.
- The MS/Ae mouse strain exhibited a higher response to B[a]P-induced micronuclei compared to the CD-1 strain.
Conclusions:
- Both peroral and intraperitoneal routes are effective for B[a]P administration in the micronucleus test, with minimal differences in genotoxic outcome.
- The MS/Ae mouse strain is a more sensitive model for detecting B[a]P genotoxicity.