The micronucleus assay as a test for the detection of aneugenic activity.
The aim of this work was to determine the usefulness of the micronucleus assay for the detection of aneugenic potential. Chemicals affecting microtubule assembly, i.e., colchicine, vinblastine sulfate and tubulazole, and chemicals affecting targets other than microtubuli, i.e., mitomycin C, cyclophosphamide and miconazole, and the clastogens azathioprine and procarbazine were administered once orally or intraperitoneally to male and female mice. Bone marrow preparations were made at 24, 48 and 72 h after dosing. All the clastogens and aneugens, except miconazole, yielded positive results in the micronucleus test. Measurements of the area of the micronuclei and their distribution clearly showed that the chemicals affecting microtubule assembly produced larger micronuclei than did the clastogens. The pattern of area distribution of the micronuclei found with cyclophosphamide and mitomycin C was between those found for the tubulin inhibitors and the clastogens. These findings indicate that the micronucleus test not only detects chemicals affecting microtubule assembly, but also can discriminate them from clastogens by measurements of the area of the micronuclei.
Vanparys
P
P
Department of Toxicology, Janssen Pharmaceutica, Beerse, Belgium.
Vermeiren
F
F
Sysmans
M
M
Temmerman
R
R
D000782:Aneuploidy; D000818:Animals; D001379:Azathioprine / Q000633:toxicity; D001853:Bone Marrow / Q000187:drug effects*; D002455:Cell Division; D003078:Colchicine / Q000633:toxicity; D003520:Cyclophosphamide / Q000633:toxicity; D004148:Dioxolanes / Q000633:toxicity; D004912:Erythrocytes / Q000187:drug effects*; D005260:Female; D008297:Male; D051379:Mice; D008825:Miconazole / Q000633:toxicity; D015162:Micronucleus Tests; D008870:Microtubules / Q000187:drug effects; D016685:Mitomycin; D008937:Mitomycins / Q000633:toxicity; D011344:Procarbazine / Q000633:toxicity; D014747:Vinblastine / Q000633:toxicity
D004148:Dioxolanes; D008937:Mitomycins; D011344:Procarbazine; D016685:Mitomycin; C040422:tubulazole; D014747:Vinblastine; D008825:Miconazole; D003520:Cyclophosphamide; D001379:Azathioprine; D003078:Colchicine