MICRONUCLEUS INDUCTION IN CYTOKINESIS-BLOCKED MOUSE BONE-MARROW CELLSIN-VITRO FOLLOWING IN-VIVO EXPOSURE TO X-IRRADIATION AND CYCLOPHOSPHAMIDE

A cytokinesis-block micronucleus (MN) method for the simultaneous but separate measurement of chromosome damage in erythroid and myeloid bon e marrow cells is described. MN induction in cytokinesis-blocked mouse bone marrow cells in vitro following in vivo exposure to x-ray or cyc lophosphamide (CP) was investigated. Immediately after whole body irra diation with acute doses of either 0, 1, 2 or 4 Gy x-rays, or 2 hr aft er treatment with either 0, 12.5, 25, or 50 mg CP/kg body weight, bone marrow cells were collected and then cultured in medium supplemented with 3.0 mu g/ml cytochalasin B for 24 hr. The binucleated cells were scored in erythroid, myeloid, lymphoid and other cells. The myeloid/er ythroid (M/E) ratio was decreased by x-irradiation or CP treatment in a dose-dependent manner. The dividing index (DI; binucleated cells/bin ucleated + mononucleated cells; %) was decreased in both erythroid and myeloid cells in the same manner. Dose-dependent increases in MN freq uency were observed following x-irradiation in both erythroid and myel oid cells. A similar dose-dependent MN induction was observed with CP. The MN frequency in myeloid cells was much greater than in erythroid cells (about 4-fold following 4 Gy exposure, and more than 10-fold aft er 50 mg/kg CP). Lymphoid and other cells were not suitable for scorin g DI and MN frequency because of insufficient numbers of binucleated c ells. These results suggest that micronuclei can be identified in both myeloid and erythroid cells and that myeloid cells are more susceptib le to x-ray or CP-induced chromosomal damage than erythroid cells as e xpressed by MN induction. (C) 1994 Wiley-Liss, Inc.