erythrocytes and splemc lymphocytes of benzene-treated mice using two molecular cytogenetic approaches: (a) fluorescence in situ hybridization with a centromeric DNA probe; and (b) staining with the calcinosis Raynaud's phenomenon-esophageal dismoblllty-sclerodactyly-telangiec

Benzene Is a widely recognized human and animal carcinogen. In spite of considerable research, relatively little Is known about the genotoxic events that accompany benzene exposure in vivo.To gain Insinjitsinto the mechanisms underlying the genotoxic effects of benzene, we have charac terized the origin of the micronuclei that are formed in bone marrow erythrocytes and splemc lymphocytes of benzene-treated mice using two molecular cytogenetic approaches: (a) fluorescence in situ hybridization with a centromeric DNA probe; and (b) staining with the calcinosis Raynaud's phenomenon-esophageal dismoblllty-sclerodactyly-telangiec taxis syndrome of scleroderma (CREST) antibody, an antibody recognlz. Ing a centromeric protein. Following the p.o. administration of benzene (220 or 440 mg/kg) to male CD-i mice, a significant increase in micronu del was observed in the bone marrow erythrocytes. In situ hybridization with a centromeric DNA probe and Immunofluorescent staining with the CREST antibody indicated that the inicronuclel in bone marrow eryth rocytes were formed from both chromosome loss and breakage The m*jorlty of the micronuclel originated from chromosome breakage. A dose-related increase in micronucleated cells was also observed in spleno cyte cultures established from these benzene-treated animals. In contrast to the bone marrow erythrocyte results, the mgjorlty of benzene-induced niicronuclei in the cytokinesis-blocked splenocytes labeled with the CREST antibody indicating that these mlcronuclel were the result of whole chromosome loss. These data demonstrate that both aneuploidy and chromosomal breakage are early genotoxic events induced by benzene or Its metabolites in vivo and also indicate that the nature of the chromo somal alterations may vary depending on the target organ or cell type.