Micronucleus test with 6-mercaptopurine monohydrate administered intraperitoneally and orally

Area of Science:

• Toxicology
• Pharmacology
• Genetics

Background:

• The route of drug administration can significantly influence its pharmacokinetic profile and subsequent toxicological effects.
• Assessing genotoxicity requires understanding how different administration methods impact the detection of DNA damage markers.

Purpose of the Study:

• To investigate the effect of administration route (intraperitoneal vs. oral) on the induction of micronucleated polychromatic erythrocytes (MNPCEs) by 6-Mercaptopurine monohydrate (6-MP).
• To compare the efficiency of 6-MP in inducing genotoxicity via different routes in two mouse strains.

Main Methods:

• Two mouse strains (MS/Ae and CD-1) were used.
• 6-Mercaptopurine monohydrate (6-MP) was administered via intraperitoneal (i.p.) and oral (p.o.) routes at selected dose ranges (i.p.: 12.5-100 mg/kg; p.o.: 25-200 mg/kg).
• Micronucleated polychromatic erythrocytes (MNPCEs) were analyzed 48 hours post-administration.

Main Results:

• 6-MP induced MNPCEs in a dose-dependent manner following i.p. administration.
• For the p.o. route, MNPCE frequencies peaked at 50 or 100 mg/kg.
• Oral administration of 6-MP resulted in a more efficient induction of MNPCEs compared to i.p. administration in both mouse strains.

Conclusions:

• The route of administration is a critical factor in the genotoxic potential of 6-MP.
• Oral administration of 6-MP demonstrates higher efficacy in inducing MNPCEs, suggesting altered bioavailability or metabolic activation compared to i.p. administration.
• These findings are crucial for accurate genotoxicity testing and risk assessment of 6-MP.