Dimethylnitrosamine-induced micronucleus formation in mouse bone marrow and spleen
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G Krishna1, M L Kropko, J C Theiss
1Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48105.
Abstract:
The present study was designed to obtain information on the kinetics of micronucleus (MN) formation following dimethylnitrosamine (DMN) treatment in mice. Male mice were injected once intraperitoneally with 50 or 100 mg/kg DMN. Bone marrow and spleen were obtained at various sacrifice time-points and processed for micronucleus analysis. The vehicle control group had 0.6 and 0.9 MN polychromatic erythrocytes (PCEs)/1000 PCEs in bone marrow and spleen, respectively. DMN, at 50 mg/kg, caused 3.8, 7.8, 8.5 and 10.2 MN PCEs/1000 PCEs in bone marrow and 8.0, 9.2, 19.3 and 32.8 MN PCEs/1000 PCEs in spleen at 12, 24, 36 and 48 h sacrifice times, respectively. A similar time-related elevation of micronucleus frequency was noted for 100 mg/kg DMN. At each sacrifice time-point, spleen PCEs had a higher micronucleus frequency than bone-marrow PCEs. In general, DMN decreased the proportion of PCEs to total erythrocytes, suggesting toxicity. Thus, this study demonstrates the clastogenic activity of DMN in both bone-marrow and spleen PCEs of mice and shows a time-related pattern in elevating DMN-induced MN PCE frequency.
Insights
Dimethylnitrosamine (DMN) exposure increases micronucleus (MN) formation in mouse bone marrow and spleen. This genotoxic effect is dose-dependent and time-related, indicating DMN
Area of Science:
- Toxicology
- Genetics
- Biomedical Research
Background:
- Dimethylnitrosamine (DMN) is a known toxicant.
- Micronucleus (MN) formation is a marker of genotoxicity.
- Understanding DMN's genotoxic kinetics is crucial for risk assessment.
Purpose of the Study:
- To investigate the time-course of micronucleus formation after DMN administration in mice.
- To compare MN induction in bone marrow and spleen following DMN exposure.
- To assess the dose-dependent genotoxic effects of DMN.
Main Methods:
- Male mice were administered single intraperitoneal injections of DMN (50 or 100 mg/kg) or vehicle control.
- Bone marrow and spleen samples were collected at various time points (12, 24, 36, 48 hours).
- Micronucleus analysis was performed on polychromatic erythrocytes (PCEs).
Main Results:
- DMN treatment significantly increased MN frequency in both bone marrow and spleen PCEs in a time-dependent manner.
- Higher DMN doses resulted in a greater elevation of MN frequency.
- Spleen exhibited a higher MN frequency compared to bone marrow at all time points.
- DMN exposure led to a decrease in the PCE to total erythrocyte ratio, suggesting toxicity.
Conclusions:
- DMN exhibits significant clastogenic activity in mouse bone marrow and spleen.
- The genotoxic effect of DMN is dose-dependent and shows a clear time-related pattern.
- Spleen is a sensitive indicator for DMN-induced genotoxicity.