A comparison of intraperitoneal injection and oral gavage in the micronucleus test with mitomycin C in mice

Area of Science:

• Genotoxicity testing
• In vivo toxicology studies
• Mammalian cell assays

Background:

• The mouse micronucleus test is a standard assay for detecting genotoxic compounds.
• Evaluating different administration routes is crucial for accurate toxicity assessment.

Purpose of the Study:

• To compare the efficacy of intraperitoneal (i.p.) injection versus oral (p.o.) gavage for mitomycin C (MMC) administration in the mouse micronucleus test.
• To establish a dose-response relationship for MMC using both administration routes.

Main Methods:

• Conducted the mouse micronucleus test using MS/Ae and CD-1 mouse strains across two laboratories.
• Administered MMC via i.p. injection and p.o. gavage at doses of 1, 2, 4, and 8 mg/kg with a 24-h sampling time.
• Determined the frequency of micronucleated polychromatic erythrocytes (MNPCEs) for each dose and route.

Main Results:

• Both i.p. injection and p.o. gavage demonstrated a clear positive dose-response relationship for MMC-induced genotoxicity in both mouse strains.
• The frequency of MNPCEs was higher with i.p. administration when expressed per mg/kg.
• This trend reversed when the dose was normalized as a percentage of the LD50, suggesting route-dependent bioavailability or toxicity.

Conclusions:

• Both intraperitoneal injection and oral gavage are effective routes for administering mitomycin C in the mouse micronucleus test.
• The choice of administration route can influence the observed genotoxic effect when expressed relative to body weight or LD50.
• Further pharmacokinetic and toxicodynamic studies may be warranted to fully elucidate the differences between administration routes.