Validation of the in vivo CD1 mouse splenocyte micronucleus test.
In order to validate the in vivo micronucleus test in mouse splenocytes using the cytokinesis block method, 14 compounds with various mechanisms of action were tested: three direct alkylating agents (mitomycin C, ethylnitrosourea, beta-propiolactone), seven indirect alkylating agents (cyclophosphamide, benzo[a]pyrene, diethylnitrosamine, dimethylnitrosamine, 4-aminophenol, 4-aminobiphenyl, 1,1-dimethylhydrazine), two intercalating agents (acridine orange, ethidium bromide) and two spindle poisons (vincristine, colchicine). Male mice were dosed once with the compound, and spleen samples were taken 2 or 14 days after treatment. A significant increase in the binucleated micronucleated splenocyte rate was observed with all the alkylating and intercalating agents at at least one sampling time. In contrast, no increase in the binucleated micronucleated splenocyte rate was observed with the spindle poisons. In conclusion, under these experimental conditions, this in vivo test seems appropriate for the detection of clastogenic compounds including compounds that cannot be detected in the bone marrow micronucleus test. The limit of this test, as expected, is the lack of detection of aneugenic compounds.
Benning
V
V
Rhône-Poulenc Rorer S.A., Centre de recherche de Vitry-Alfortville, Départment Sécurité du Médicament, Vitry sur Seine, France.
Brault
D
D
Duvinage
C
C
Thybaud
V
V
Melcion
C
C
D000477:Alkylating Agents / Q000633:toxicity; D000818:Animals; D007364:Intercalating Agents / Q000633:toxicity; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects; D015162:Micronucleus Tests / Q000379:methods* / Q000706:statistics & numerical data; D009153:Mutagens / Q000633:toxicity; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D008941:Spindle Apparatus / Q000187:drug effects; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013997:Time Factors
D000477:Alkylating Agents; D007364:Intercalating Agents; D009153:Mutagens