Characterization of genetic instability in radiation- and benzene-induced murine acute leukemia

This study, using the CBA/Ca mouse as a model, compares genetic lesions ass ociated with radiation- and benzene-induced acute leukemias. Specific types of leukemia included in the analyses are radiation-induced acute myeloid l eukemia (ML), and benzene-induced lymphoblastic leukemias, lymphomas, or mi x-lineage leukemias. These leukemias have histopathological characteristics similar to those seen in human acute leukemias. G-band cytogenetic analysi s showed that specific deletions involving regions D-E of one copy of mouse chromosome 2 [del(2)(D-E)] were frequently associated in both radiation- a nd benzene-induced acute leukemias. In addition, translocations of chr2(D-E ) were also observed in some cases. These results suggest an important role of chr2(D-E) deletions and translocations in the development of radiation- and benzene-induced murine acute leukemias. Fluorescence in situ hybridiza tion with DNA probes specific for 2(D-E), constructed in our laboratory by means of chromosomal microdissection and PCR amplification, also demonstrat e 2(D-E) deletions and/or translocations in these leukemic cells. Aneuploid y of chromosomes 3, 15, 16, and Y were also frequently detected in benzene- induced leukemic cells with or without lesions on chr2. These cytogenetic f indings support the previous observations that metabolites of benzene lead to spindle-fiber disruption or abnormal cytokinesis in exposed animals. In summary, genetic instabilities observed in leukemic cells isolated from mic e that had developed leukemia after exposure to radiation or benzene are sy ntenic with those frequently detected in patients with myelodysplastic synd rome, acute ML, and acute lymphoblastic leukemia. Thus, the CBA/Ca mouse ha s several characteristics that make it an excellent model for the study of radiation or benzene leukemogenesis in humans. (C) 1999 Elsevier Science B. V. All rights reserved.