The ProtéoSeine lab contributed to a new article published in Journal of Hazardous Material:
Abstract:
Benzene (BZ) is a pervasive environmental and occupational carcinogen whose leukemogenicity depends on metabolic activation into reactive intermediates, notably 1,4-benzoquinone (BQ). While genotoxic effects such as DNA damage and chromosomal instability have been extensively documented, growing evidence highlights a central role for epigenetic dysregulation in BZ-induced hematotoxicity. In this study, we identify a novel molecular mechanism linking BZ metabolism to epigenetic dysfunction. We demonstrate that BQ irreversibly inhibits the histone H3K18 acetyltransferase activity of CREB-binding protein (CREBBP/CBP), a key epigenetic regulator essential for normal hematopoiesis and tumor suppression. Mechanistically, BQ rapidly forms covalent adducts with critical cysteine residues, notably within the RING and PHD Zn²⁺-finger domains of CBP, thereby impairing its catalytic activity. Both in vitro and cellular models show that BQ exposure markedly reduces CBP acetyltransferase activity, accompanied by decreased levels of the epigenetic mark H3K18Ac. These findings identify CBP as a direct molecular target of benzene metabolites and reveal an epigenetic mechanism that may contribute to the hematotoxic and leukemogenic effects of BZ.
Xiao H, Duval R, Li Z, Zhang W, Durand L, Coste-Sarguet L, Bui LC, Haddad I, Vinh J, Cochard V, Chevreux G, Dupret JM, Dulphy N, Chomienne C, Wang L, Rodrigues-Lima F, Guidez F. CBP inhibition and histone H3K18 hypoacetylation induced by the hematotoxic benzene metabolite 1,4-benzoquinone. J Hazard Mater. 2026 Oct 12;518:143883. doi: 10.1016/j.jhazmat.2026.143883. Epub ahead of print. PMID: 42945668.