{"id":"df09b352-2fba-5632-9ce2-b535815931a4","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:cancer-hat-no-rescue","predicate":"no_detected_change_in_recorded_comparison","statement":"ALCAR did not rescue DNA-damage sensitivity when histone acetyltransferase activity was inhibited.","claim_class":"observational","status":"source_recorded","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"cef1c8b9-cbc1-5908-a365-4647037f32ab","mechanism_event_label":"ALCAR did not rescue DNA-damage sensitivity when histone acetyltransferase activity was inhibited.","subject":{"id":"5ce394a9-6ec6-56dd-866f-37d85c0556e4","slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"},"object":{"id":"bde591f9-f239-51be-9a7e-62bd66227719","slug":"human-cancer-alcar-drug-survival","display_name":"Human cancer-cell survival with DNA-damaging treatment","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"cef1c8b9-cbc1-5908-a365-4647037f32ab","stable_key":"e3f6ce02-0bd7-5103-acc1-68503ab6751b:cancer-hat-no-rescue-event","event_type":"experimental_observation","label":"ALCAR did not rescue DNA-damage sensitivity when histone acetyltransferase activity was inhibited.","description":"### cancer-hat-no-rescue\n\nALCAR did not rescue DNA-damage sensitivity when histone acetyltransferase activity was inhibited.\nSupplying substrate failed when downstream acetylation machinery was blocked. The tested HAT inhibitor and individual drug concentrations are not fully extracted here; no universal inhibitor equivalence is asserted.\nModel and exposure: CCNE1-driven human cell models; HAT inhibition plus DNA-damaging agents; Extended Data Fig. 5.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5ce394a9-6ec6-56dd-866f-37d85c0556e4","slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"},"role":"tested factor","stoichiometry":null,"state_label":"ALCAR plus HAT inhibition and DNA-damaging treatment","sequence_order":0,"notes":""},{"entity":{"id":"bde591f9-f239-51be-9a7e-62bd66227719","slug":"human-cancer-alcar-drug-survival","display_name":"Human cancer-cell survival with DNA-damaging treatment","entity_type_key":"cellular_process"},"role":"measured outcome","stoichiometry":null,"state_label":"no_detected_change","sequence_order":1,"notes":""},{"entity":{"id":"e4c89513-41b4-54d5-9dbd-0baee186b26a","slug":"olaparib","display_name":"Olaparib","entity_type_key":"drug"},"role":"DNA-damaging treatment context","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"bdb83796-78cf-5b54-9ca6-4dab19b33600","slug":"cisplatin","display_name":"Cisplatin","entity_type_key":"drug"},"role":"DNA-damaging treatment context","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_access","value_text":"Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_contrast","value_text":"{\"intervention\": \"ALCAR plus HAT inhibition and DNA-damaging treatment\", \"comparator\": \"Same HAT inhibition and DNA-damaging treatment without ALCAR\", \"endpoint\": \"ALCAR did not rescue DNA-damage sensitivity when histone acetyltransferase activity was inhibited.\", \"effect_direction\": \"no_detected_change\", \"combination\": \"single\", \"conditions\": []}","comparator":null,"unit":null,"notes":"Explicit extracted experimental comparison; source-derived draft.","entity":null},{"dimension":"experimental_model","value_text":"CCNE1-driven human cell models; HAT inhibition plus DNA-damaging agents; Extended Data Fig. 5.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"interpretation_status","value_text":"Source-derived curation with stated access limits; ungraded, not independent replication.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Acetyl-L-carnitine collection; exact intervention and molecular form govern interpretation.","comparator":null,"unit":null,"notes":"","entity":{"slug":"acetylcarnitine","display_name":"Acetyl-L-carnitine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"ALCAR did not rescue DNA-damage sensitivity when histone acetyltransferase activity was inhibited.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"source_locator","value_text":"Reviewed reference cancer-hat-no-rescue; Supplying substrate failed when downstream acetylation machinery was blocked. The tested HAT inhibitor and individual drug concentrations are not fully extracted here; no universal inhibitor equivalence is asserted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"f818a96a-c2d1-59e9-a92d-7e5948e82301","evidence_kind":"source_excerpt","locator":"Lines 328-334","start_line":328,"end_line":334,"excerpt":"### cancer-hat-no-rescue\n\nALCAR did not rescue DNA-damage sensitivity when histone acetyltransferase activity was inhibited.\nSupplying substrate failed when downstream acetylation machinery was blocked. The tested HAT inhibitor and individual drug concentrations are not fully extracted here; no universal inhibitor equivalence is asserted.\nModel and exposure: CCNE1-driven human cell models; HAT inhibition plus DNA-damaging agents; Extended Data Fig. 5.\nLimitations: Limited to the recorded preparation, model, exposure and endpoint. Does not establish a human dietary deficiency, clinical benefit or unique molecular mediation.\nReference: αKG-mediated carnitine synthesis drives DNA repair via histone acetylation. | 2026 | https://pubmed.ncbi.nlm.nih.gov/42203879/ | https://pmc.ncbi.nlm.nih.gov/articles/PMC13307467/ | https://doi.org/10.1038/s41586-026-10584-7 | Access: Primary full text: relevant Results/Methods and figure descriptions reviewed; supplements only where explicitly stated.","model_system":"CCNE1-driven human cell models; HAT inhibition plus DNA-damaging agents; Extended Data Fig. 5.","directness":"reported_statement","verification_status":"source_recorded","notes":"Original paraphrase in the retained reviewed reference, not a verbatim primary-paper quotation. Access level is explicit.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"2588f904-245a-597a-8a12-65118013fb90","stable_key":"import-e3f6ce02-0bd7-5103-acc1-68503ab6751b","title":"Acetyl-L-carnitine: detailed mechanisms of action (reviewed 6 October 2026)","document_type":"imported_text","citation_label":"AI-assisted original review of primary studies and clearly identified official records. Exact primary access is stated; no independent replication is claimed.","file_path":"","sha256":"84cc82d6fbb0fd5d73c4ce779e9f88e7f0184ba2d29b18ad0f153815380f2975","revision_id":"dac7a950-dbe5-5c7a-9c70-2ea711d5c71a","review_status":"source_recorded","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}