An in vivo/in vitro method for assessing micronucleus and chromosome aberration induction in XXXX bone marrow and spleen. 2. Studies with @entity5805 and @entity1138 .

@entity1138 @entity5805 @entity1139 @entity7422 @entity35 @entity2008
An in vivo/in vitro system using @entity35 bone marrow cells and spleen cells to assess micronucleus (MN) and @entity2008 ( @entity2008 ) simultaneously (Moore et al., 1995) was further developed. In two separate experiments, two @entity35 /dose/experiment were treated i.p. with 0, 5, 10 and 15 mg @entity5805 (CA)/kg or with @entity1138 ( @entity1139 ) at 0, 1, 2, 4 mg/kg (experiment 1) or 0, 4, 6, and 8 mg/kg (experiment 2) and killed 6 h later. Cultures were then established in the presence of growth stimulants ( @entity7422 and granulocyte-macrophage colony stimulating factor for bone marrow; lipopolysaccharide and concanavalin A for spleen) and cytochalasin B, a cytokinesis inhibitor. Bone marrow cells were harvested 24 h after establishment of cultures, while spleen cells were harvested at 48 h. In addition, spleen cells were concurrently assayed for chromosome aberrations. With the MN endpoint, spleen cells appeared more sensitive than bone marrow cells to the effects of CA due both to a lower background and an increased response. For @entity1139 , bone marrow cells exhibited both a higher background of MN and a greater numerical response than did spleen cells. However, on the basis of a fold-increase over control values, spleen cells were more sensitive than bone marrow cells. In general, the MN endpoint appeared more sensitive than the @entity2008 in spleen cells after treatment with CA or @entity1139 . Thus, the approach described here shows greater potential in detecting genotoxicity.
