SYNERGISTIC INCREASE IN CHROMOSOMAL BREAKAGE WITHIN THE EUCHROMATIN INDUCED BY AN INTERACTION OF THE BENZENE METABOLITES PHENOL AND HYDROQUINONE IN MICE

The hematopoietic and carcinogenic effects of benzene may result from an interaction of various benzene metabolites, Following the co-admini stration of phenol and hydroquinone, a synergistic increase in myeloto xicity and genotoxicity has been observed in the bone marrow of mice. To understand the mechanisms underlying these synergistic genotoxic ef fects we have studied the origin of micronuclei (MN) formed in bone ma rrow erythrocytes following the co-administration of these two metabol ites, Phenol and hydroquinone were administered to male CD-1 mice by i .p. injection three times at 24 h intervals, The frequency of MN was e valuated in bone marrow cells harvested 24 h following the final dose, A marked increase in MN was observed in mice co-administered phenol a nd hydroquinone, which was significantly greater than that observed wi th the individual metabolites, Labeling with the CREST antibody and mu lticolor fluorescence in situ hybridization with the mouse major and m inor satellite probes indicated that both chromosomal loss and breakag e had occurred, The major increase in MN induced by the phenol and hyd roquinone combination originated from breakage in the euchromatic regi on of the mouse chromosomes, The origin of MN in mice co-administered phenol and hydroquinone differed substantially from that induced by hy droquinone alone, but was almost identical to that seen in MN from ben zene-treated mice. These results strongly support the hypothesis that interactive effects among benzene metabolites play an important role i n the genotoxic and carcinogenic effects of benzene.