{"id":"fb7d3d73-db5b-5105-a8b7-83e29eb3c8e4","stable_key":"4d8e4781-3878-5818-8d0a-7dbd6e024555:chromium-gsh-chromate-mutagenesis","predicate":"modulates","statement":"Chromate reduction with 2 mM glutathione produced weak plasmid mutagenicity; 5 mM glutathione produced about four times the mutation yield per DNA adduct.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e523c266-0d84-57b5-aa20-a0cc10f6289c","mechanism_event_label":"More glutathione did not simply mean less damage in this chemical system.","subject":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"object":{"id":"6050eb6a-a18d-5d2e-b033-449dc1152956","slug":"chromium-induced-dna-mutagenesis","display_name":"Mutation induction by chromium-treated DNA","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e523c266-0d84-57b5-aa20-a0cc10f6289c","stable_key":"4d8e4781-3878-5818-8d0a-7dbd6e024555:chromium-gsh-chromate-mutagenesis-event","event_type":"biochemical_relationship","label":"More glutathione did not simply mean less damage in this chemical system.","description":"Chromate reduction with 2 mM glutathione produced weak plasmid mutagenicity; 5 mM glutathione produced about four times the mutation yield per DNA adduct.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"15b3e015-2780-5848-a962-64c9f67e8087","slug":"chromate","display_name":"Chromate / chromium(VI) oxyanion","entity_type_key":"ion"},"role":"toxic_exposure","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b44c9e27-4bbb-52d3-a022-14cddded5073","slug":"glutathione","display_name":"GSH","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6050eb6a-a18d-5d2e-b033-449dc1152956","slug":"chromium-induced-dna-mutagenesis","display_name":"Mutation induction by chromium-treated DNA","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/chromium-research/18808157.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ed2c80b5da41d110da38bc0ed29d900d1d33f4180b64e13cb9b24ae7da5e1cdb\", \"start_char\": 0, \"end_char\": 1724, \"text_sha256\": \"ed2c80b5da41d110da38bc0ed29d900d1d33f4180b64e13cb9b24ae7da5e1cdb\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Cell-free chromate reduction followed by plasmid replication in human fibroblasts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"2 versus 5 mM glutathione with Cr(VI)","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Toxicology assay, not oral chromium exposure. Proposed crosslink identities depend on preparation and analytical methods; later work questions some pre-reacted ternary-adduct preparations.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Chromium research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"chromium","display_name":"Chromium","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Chemical system with human fibroblast mutagenicity readout","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"More glutathione did not simply mean less damage in this chemical system.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[chromium-p18808157] Reduction with glutathione is a weakly mutagenic pathway in chromium(VI) metabolism. (2008). https://pubmed.ncbi.nlm.nih.gov/18808157/ DOI: 10.1021/tx800265g","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"DNA reaction mixture and reporter plasmid","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"619b9064-e1cc-5ee8-8fb9-da9d512d27c3","evidence_kind":"source_excerpt","locator":"Lines 1160-1171","start_line":1160,"end_line":1171,"excerpt":"### chromium-gsh-chromate-mutagenesis\nChromate reduction with 2 mM glutathione produced weak plasmid mutagenicity; 5 mM glutathione produced about four times the mutation yield per DNA adduct.\nCondition category: normal\nnutrient_topic: Chromium research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: More glutathione did not simply mean less damage in this chemical system.\norganism: Chemical system with human fibroblast mutagenicity readout\ntissue_or_cell_type: DNA reaction mixture and reporter plasmid\nexperimental_model: Cell-free chromate reduction followed by plasmid replication in human fibroblasts\nlimitations: Toxicology assay, not oral chromium exposure. Proposed crosslink identities depend on preparation and analytical methods; later work questions some pre-reacted ternary-adduct preparations.\nexposure: 2 versus 5 mM glutathione with Cr(VI)\nevidence_span: {\"source_cache\": \"artifacts/chromium-research/18808157.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ed2c80b5da41d110da38bc0ed29d900d1d33f4180b64e13cb9b24ae7da5e1cdb\", \"start_char\": 0, \"end_char\": 1724, \"text_sha256\": \"ed2c80b5da41d110da38bc0ed29d900d1d33f4180b64e13cb9b24ae7da5e1cdb\"}\n[chromium-p18808157] Reduction with glutathione is a weakly mutagenic pathway in chromium(VI) metabolism. 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