{"doi":"10.17615/xwf7-bh83","title":"Iminohydantoin Lesion Induced in DNA by Peracids and Other Epoxidizing Oxidants","abstract":"The oxidation of guanine to 5-carboxamido-5-formamido-2-iminohydantoin (2-Ih) is shown to be a major transformation in the oxidation of the single-stranded DNA 5-mer d(TTGTT) by m-CPBA and DMDO as a model for peracid oxidants and in the oxidation of the 5-base pair duplex d[(TTGTT)·(AACAA)] with DMDO. 2-Ih has not been reported as an oxidative lesion at the level of single/double-stranded DNA or at the nucleoside/nucleotide level. The lesion is stable to DNA digestion and chromatographic purification suggesting that 2-Ih may be a stable biomarker in vivo. The oxidation products have been structurally characterized and the reaction mechanism probed by oxidation of the monomeric species dGuo, dGMP and dGTP. DMDO selectively oxidizes the guanine moiety of dGuo, dGMP and dGTP to 2-Ih, and both peracetic and m-chloroperbenzoic acids exhibit the same selectivity. The presence of the glycosidic bond results in the stereoselective induction of an asymmetric center at the spiro carbon to give a mixture of diastereomers, with each diastereomer in equilibrium with a minor conformer through rotation about the formamido C-N bond. Labeling studies with 18O2-m-CPBA and H218O to determine the source of the added oxygen atoms have established initial epoxidation of the guanine 4-5 bond with pyrimidine ring contraction by an acyl 1,2-migration of guanine carbonyl C6 to form a transient dehydrodeoxyspiroiminodihydantoin followed by hydrolytic ring opening of the imidazolone ring. Consistent with the proposed mechanism, no 8-oxoguanine was detected as a product of the oxidations of the oligonucleotides or monomeric species mediated by DMDO or the peracids. The 2-Ih base thus appears to be a pathway-specific lesion generated by peracids and possibly other epoxidizing agents and holds promise as a potential biomarker.","journal":"INDIGO (University of Illinois at Chicago)","year":2020,"id":136178,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9487,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":542905,"name":"Wenjie Ye","orcid":"0000-0001-6065-9905","position":1,"is_corresponding":false},{"id":543805,"name":"Nedyalka Dicheva","orcid":null,"position":2,"is_corresponding":false},{"id":505011,"name":"Roel M. Schaaper","orcid":"0000-0003-1344-3196","position":3,"is_corresponding":false},{"id":233675,"name":"Gunnar Boysen","orcid":"0000-0001-8364-9881","position":4,"is_corresponding":false},{"id":595122,"name":"Diana E. Degen","orcid":null,"position":5,"is_corresponding":false},{"id":595123,"name":"Viorel Mocanu","orcid":null,"position":6,"is_corresponding":false},{"id":537969,"name":"Avram Gold","orcid":"0000-0003-1383-6635","position":7,"is_corresponding":false},{"id":594582,"name":"Karl M. Koshlap","orcid":"0000-0002-4080-2150","position":8,"is_corresponding":false},{"id":595124,"name":"R. Sangaiah","orcid":null,"position":9,"is_corresponding":false},{"id":595125,"name":"Kiruthika Jayaraj","orcid":null,"position":10,"is_corresponding":false},{"id":524531,"name":"Carol E. Parker","orcid":null,"position":11,"is_corresponding":false},{"id":65890,"name":"Kenneth B. Tomer","orcid":null,"position":12,"is_corresponding":false},{"id":537968,"name":"Louise M. Ball","orcid":"0000-0002-1758-3228","position":13,"is_corresponding":false},{"id":44758,"name":"Jason Williams","orcid":"0000-0002-3804-2594","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:48.793683Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}