The benzene metabolites hydroquinone and catechol act in synergy to inducedose-dependent hypoploidy and-5q31 in a human cell line

Chronic exposure to high concentrations of benzene is associated with an in creased incidence of myelodysplastic syndrome (MDS) and acute myelogenous l eukemia (AML), Studies of patients occupationally exposed to benzene show a pattern of cytogenetic aberrations involving loss of all or part of chromo somes 5 and/or 7 as well as trisomy 8 and we have previously reported that hydroquinone (HQ) induces deletions of 5, 7 and 8. Benzene metabolism is a requirement for bone marrow toxicity and the phenolic metabolites, HQ and c atechol (CAT), have been implicated in benzene hematotoxicity, A research p roject was designed to determine whether CAT by itself and in conjunction w ith HQ could directly induce loss of chromosome 5 and/or 7 and gain of chro mosome 8. Using fluorescence in situ hybridization with chromosome-specific 5, 7, and 8 probes we demonstrate that 5 to 150 uM CAT does not produce ch romosomal aberrations, however CAT and 25 uM HQ can act in synergy to induc e dose dependent loss of these chromosomes. In addition HQ/CAT selectively induces -5q which is not observed for HQ only. These results demonstrate fo r the first time that CAT/HQ act in synergy to induce specific chromosome l oss found in secondary MDS/AML.