title: Teratogenic activity of HDAC inhibitors.
abstract: Modification of the terminal tails of histones is considered one of the documented mechanisms for epigenetic control of gene expression. Histone deacetylase inhibitors (HDACi) lead to a state of hyperacetylation of histone, a condition that can affect normal gene transcription. Furthermore, HDACi have many other protein targets involved in regulation of gene expression, cell proliferation and cell death. For these properties some HDACi are nowadays used as anticancer drugs with promising results. Several molecules with HDACi properties (valproic acid, trichostatin A, apicidin, MS-275, sodium butyrate, boric acid, salicylic acid) have been found to induce congenital malformations associated with hyperacetylation of histones in the target organs. Cell death is the major event in the target organs a few hours after embryonic exposure to HDACi. Gene deregulation, oxidative stress, DNA demethylation, and/or retinoic acid imbalance are the modes of action postulated for HDACi-induced teratogenesis.
authors: Erminio
authors: E
authors: Giavini
authors: Università degli Studi di Milano, Department of Biosciences, via Celoria 26, I-20133 Milano, Italy. erminio.giavini@unimi.it.
authors: Elena
authors: E
authors: Menegola
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects* / Q000502:physiology; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000009:adverse effects / Q000633:toxicity*; D006801:Humans; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000378:metabolism; D013723:Teratogens / Q000633:toxicity*
chemical_list: D056572:Histone Deacetylase Inhibitors; D013723:Teratogens