Assessment of 1,2-dimethylhydrazine in bone marrow micronucleus assay: variations in protocol and response.
The effect of variations in experimental protocol on the assessment of the genotoxicity of 1,2-dimethylhydrazine (DMH) in the bone marrow micronucleus assay was determined. The incidence of micronuclei (MN) in the bone marrow of CBA mice treated with DMH (either intraperitoneally (i.p.) or orally) was found to be significantly greater than that observed in C57B1/6J mice using the same dose and dosing regimen. With i.p. injection, DMH, at doses of 20 and 50 mg/kg, was found to be positive in the bone marrow MN test in CBA mice only. In C57B1/6J mice, DMH (i.p.) was found to be positive at only the 50 mg/kg dose. With oral administration, DMH was positive in the MN test only at the 50 mg/kg dose and only in CBA mice. No significant difference in the percentage of MN was observed when 300, 500, or 1,000 polychromatic erythrocytes (PCEs) were scored following a single treatment of DMH. Cyclophosphamide (CY) was found to induce a dose-dependent increase in the percentage of MN observed in the bone marrow of C57B1/6J mice. DMH tested positive in the colon nuclear aberration (NA) assay in both strains of mice using both i.p. and oral routes of administration, although C57B1/6J mice were found to be more sensitive than CBA mice. No significant difference was observed regarding the percentage of NAs observed in the colon between mice injected i.p. or orally gavaged.
Goldberg
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Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Canada.
Schop
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D019813:1,2-Dimethylhydrazine; D000284:Administration, Oral; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D001854:Bone Marrow Cells; D002273:Carcinogens; D002470:Cell Survival; D003106:Colon / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology; D004127:Dimethylhydrazines / Q000008:administration & dosage / Q000633:toxicity*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D015162:Micronucleus Tests / Q000379:methods*; D009152:Mutagenicity Tests / Q000379:methods; D013045:Species Specificity; D013194:Staining and Labeling
D002273:Carcinogens; D004127:Dimethylhydrazines; D003520:Cyclophosphamide; D019813:1,2-Dimethylhydrazine