title: Benzene metabolites block gap junction intercellular communication. Role in hematotoxicity and leukemia?
abstract: A metabolite of benzene, trans,trans-muconaldehyde (MUC) was found to be a strong inhibitor of gap junction intercellular communication (GJIC) with potency similar to that of chlordane. Hydroquinone and the MUC metabolite OH-M-CHO were also strong inhibitors of GJIC. The other MUC metabolites tested, CHO-M-COOH and OH-M-COOH had weak effects on GJIC, while COOH-M-COOH had no effect. Benzene showed no effect on GJIC. The relative potency of the metabolites on GJIC is similar to what is observed with regard to hematotoxic effects. The effect of MUC on GJIC took place in parallel with a strong cellular loss of connexin 43. Substances found to inhibit connexin 43 dependent GJIC have been shown to disrupt normal hematopoietic development. The finding that benzene metabolites interfere with gap junction functionality, and especially the loss of connexin 43 induced by MUC, should be considered concerning the mechanism of benzene-induced hematotoxicity.
authors.affiliation: Institute for Cancer Research, Norwegian Radium Hospital, Oslo, Norway. edgarr@labmed.uio.no
authors.forename: Edgar
authors.initials: E
authors.lastname: Rivedal
authors.forename: Gisela
authors.initials: G
authors.lastname: Witz
mesh_terms: D000447:Aldehydes / Q000378:metabolism / Q000633:toxicity*; D000818:Animals; D001554:Benzene / Q000378:metabolism / Q000633:toxicity*; D002450:Cell Communication / Q000187:drug effects*; D002460:Cell Line; D017629:Gap Junctions / Q000187:drug effects* / Q000378:metabolism; D006402:Hematologic Diseases / Q000378:metabolism; D006873:Hydroquinones / Q000633:toxicity*; D007938:Leukemia / Q000378:metabolism
chemical_list: D000447:Aldehydes; D006873:Hydroquinones; C034476:muconaldehyde; D001554:Benzene; C031927:hydroquinone