Dimethylnitrosamine-induced micronucleus formation in mouse bone marrow and spleen.
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.
Krishna
G
G
Department of Pathology and Experimental Toxicology, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI 48105.
Kropko
M L
ML
Theiss
J C
JC
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D004128:Dimethylnitrosamine / Q000633:toxicity*; D007700:Kinetics; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D015162:Micronucleus Tests / Q000379:methods*; D013154:Spleen / Q000187:drug effects*; D013997:Time Factors
D004128:Dimethylnitrosamine