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The broad-spectrum herbicide atrazine (2-chloro-4-[ethylamino]-6-[isopropylamino]-1, 3, 5-triazine) and its metabolites are known to form protein adducts, but the formation of atrazine\u2013histone adducts has not been studied. In this study, a bottom-up proteomics analysis method was optimized and applied to identify histone adduction by atrazine in vitro\n                    <jats:italic>.<\/jats:italic>\n                    Whole histones of calf thymus or human histone H3.3 were incubated with atrazine. After solvent-based protein precipitation, the protein was digested by trypsin\/Glu-C and the resulting peptides were analyzed by high-resolution mass spectrometry using an ultra-high-performance liquid chromatograph interfaced with a quadrupole Exactive-Orbitrap mass spectrometer. The resulting tryptic\/Glu-C peptide of DTNLCAIHAK from calf thymus histone H3.1\u00a0or human histone H3.3 was identified with an accurate mass shift of \u2009+179.117\u00a0Da in atrazine incubated samples. It is deduced that a chemical group with an elemental composition of C\n                    <jats:sub>8<\/jats:sub>\n                    H\n                    <jats:sub>13<\/jats:sub>\n                    N\n                    <jats:sub>5<\/jats:sub>\n                    (179.1171\u00a0Da) from atrazine adducted with calf thymus histone H3.1 or human histone H3.3. It was confirmed by MS\/MS analysis that the adduction position was at its cysteine 110 residue. Time- and concentration-dependent assays also confirmed the non-enzymatic covalent modification of histone H3.3 by atrazine in vitro. Thus, the potential exists that atrazine adduction may lead to the alteration of histones that subsequently disturbs their normal function.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s00216-023-04545-6","type":"journal-article","created":{"date-parts":[[2023,1,20]],"date-time":"2023-01-20T14:59:14Z","timestamp":1674226754000},"page":"1497-1504","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Bottom-up proteomics analysis for adduction of the broad-spectrum herbicide atrazine to histone"],"prefix":"10.1007","volume":"415","author":[{"given":"Shaogang","family":"Chu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Letcher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,1,20]]},"reference":[{"key":"4545_CR1","doi-asserted-by":"publisher","first-page":"532","DOI":"10.3389\/fchem.2019.00532","volume":"7","author":"J Nunes","year":"2019","unstructured":"Nunes J, Charneira C, Nunes C, Gouveia-Fernandes S, Serpa J, Morello J, Antunes AMM. 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