title: The benzene metabolites hydroquinone and catechol act in synergy to induce dose-dependent hypoploidy and -5q31 in a human cell line.
abstract: Chronic exposure to high concentrations of benzene is associated with an increased incidence of myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Studies of patients occupationally exposed to benzene show a pattern of cytogenetic aberrations involving loss of all or part of chromosomes 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 catechol (CAT), have been implicated in benzene hematotoxicity. A research project was designed to determine whether CAT by itself and in conjunction with HQ could directly induce loss of chromosome 5 and/or 7 and gain of chromosome 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 chromosomal aberrations, however CAT and 25 uM HQ can act in synergy to induce dose dependent loss of these chromosomes. In addition HQ/CAT selectively induces -5q which is not observed for HQ only. These results demonstrate for the first time that CAT/HQ act in synergy to induce specific chromosome loss found in secondary MDS/AML.
authors.affiliation: Molecular Toxicology and Environmental Health Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver 80262, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Stillman
authors.forename: M
authors.initials: M
authors.lastname: Varella-Garcia
authors.forename: R D
authors.initials: RD
authors.lastname: Irons
mesh_terms: D001554:Benzene / Q000633:toxicity*; D002396:Catechols / Q000633:toxicity*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics; D002872:Chromosome Deletion; D002895:Chromosomes, Human, Pair 5 / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000139:chemically induced / Q000235:genetics; D009190:Myelodysplastic Syndromes / Q000139:chemically induced / Q000235:genetics; D011003:Ploidies; D014407:Tumor Cells, Cultured
chemical_list: D002396:Catechols; D001554:Benzene; C034221:catechol