title: Distinct area distribution differences of micronuclei induced by clastogenic and aneuploidogenic chemicals in the bone marrow of the CD-1 mouse.
abstract: To distinguish between aneuploidogenic and clastogenic effects of test chemicals, area distributions of micronuclei (MN) in polychromatic erythrocytes (PE) from the mouse bone marrow were measured using an image analysis system. Triethylenemelamine (TEM), cytosine-beta-D-arabinofuranoside (ara-C), urethane (URT), cyclosphamide (CP), mitomycin C (MMC), colcemid (COL) and tubulazole C (TUB) were investigated for the induction of micronucleus area distributions. The area distribution of micronuclei of untreated mice was also determined. Reproducible small differences between the clastogens and the aneuploidogens were observed after measuring 1100-1200 micronuclei. A common feature of the distribution curves was a shoulder region in the same area range for all clastogens. The aneuploidogens COL and TUB showed a plateau (= wide peak) in this clastogenic shoulder region. For all clastogens, the integrated area of shoulder over a fitted function (shoulder strength) was evaluated. MMC and CP, thought to have some aneuploidogenic potential, showed an increased shoulder strength compared to TEM, ara-C and URT. The control area distribution had no similarities to the area distribution of either clastogens or aneuploidogens. In a further experiment, we attempted to correlate the size of micronuclei determined after treatment with the aneuploidogenic chemicals to the size of whole chromosomes. Micronuclei found by image analysis which bear chromosome-like structures (judged by light microscopy) were manually identified. This selection of micronuclei was area-distributed to determine the mean size of these micronuclei. None of the peaks and plateaus in the area distributions obtained with the aneuploidogenic chemicals could be attributed to the size of a chromosome.
authors.affiliation: Sandoz Pharma Ltd., Basel, Switzerland.
authors.forename: B M
authors.initials: BM
authors.lastname: Schneider
authors.forename: F E
authors.initials: FE
authors.lastname: Würgler
authors.forename: F
authors.initials: F
authors.lastname: Romagna
mesh_terms: D000782:Aneuploidy; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects*; D001854:Bone Marrow Cells; D003520:Cyclophosphamide / Q000633:toxicity; D008297:Male; D051379:Mice; D048629:Micronuclei, Chromosome-Defective; D015162:Micronucleus Tests; D016685:Mitomycin / Q000633:toxicity; D009153:Mutagens / Q000633:toxicity*
chemical_list: D009153:Mutagens; D016685:Mitomycin; D003520:Cyclophosphamide