{"id":"b30766fb-bfc5-55e3-9c72-9935b4e3cba2","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-nitrous-oxide-marrow","predicate":"prolonged_exposure_associated_with_megaloblastic_marrow","statement":"All eight patients receiving nitrous oxide/oxygen for 24 hours had megaloblastic marrow and abnormal dU suppression; five unexposed patients had normoblastic marrow and normal assays.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"e23ae52e-1c6a-5755-a058-833dedb9f2eb","mechanism_event_label":"The exposed marrow behaved as though a B12-linked DNA-synthesis step was impaired.","subject":{"id":"e2fe2626-86ee-54bf-b85c-540ef5567fde","slug":"nitrous-oxide","display_name":"Nitrous oxide","entity_type_key":"small_molecule"},"object":{"id":"cd3712c4-cc82-5c71-8df8-9d82d60ce397","slug":"bone-marrow-megaloblastosis","display_name":"Bone marrow megaloblastosis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e23ae52e-1c6a-5755-a058-833dedb9f2eb","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:b12-nitrous-oxide-marrow-event","event_type":"observed_intervention","label":"The exposed marrow behaved as though a B12-linked DNA-synthesis step was impaired.","description":"All eight patients receiving nitrous oxide/oxygen for 24 hours had megaloblastic marrow and abnormal dU suppression; five unexposed patients had normoblastic marrow and normal assays.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b6d9b937-895d-5e0a-8cc5-0454a0b7d373","slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"},"role":"functionally_implicated_nutrient","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e4eb7b08-dbef-5923-aa11-4e76c63bb482","slug":"deoxyuridine-suppression-assay","display_name":"Deoxyuridine suppression assay","entity_type_key":"cellular_process"},"role":"measured_readout","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e2fe2626-86ee-54bf-b85c-540ef5567fde","slug":"nitrous-oxide","display_name":"Nitrous oxide","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"cd3712c4-cc82-5c71-8df8-9d82d60ce397","slug":"bone-marrow-megaloblastosis","display_name":"Bone marrow megaloblastosis","entity_type_key":"cellular_process"},"role":"target","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":"cross_nutrient","value_text":"B12-dependent folate handling connects to DNA synthesis; linked existing MTR evidence supplies the molecular context.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Prospective perioperative study in 22 patients undergoing cardiac bypass surgery.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Nitrous oxide/oxygen for 24 hours, during surgery only, or no nitrous oxide; marrow morphology and deoxyuridine suppression assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The clinical experiment did not directly measure intracellular cobalamin oxidation state or prove that serum B12 stores were depleted.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The exposed marrow behaved as though a B12-linked DNA-synthesis step was impaired.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[b12-amess1978] Megaloblastic haemopoiesis in patients receiving nitrous oxide (1978). https://pubmed.ncbi.nlm.nih.gov/79709/ DOI: 10.1016/s0140-6736(78)92941-0","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Human bone marrow","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":"8af3a805-9b4f-5ee2-a7c9-22b4f025be91","evidence_kind":"source_excerpt","locator":"Lines 1709-1720","start_line":1709,"end_line":1720,"excerpt":"### b12-nitrous-oxide-marrow\nAll eight patients receiving nitrous oxide/oxygen for 24 hours had megaloblastic marrow and abnormal dU suppression; five unexposed patients had normoblastic marrow and normal assays.\nCondition category: machinery_impairment\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The exposed marrow behaved as though a B12-linked DNA-synthesis step was impaired.\norganism: Homo sapiens\ntissue_or_cell_type: Human bone marrow\nexperimental_model: Prospective perioperative study in 22 patients undergoing cardiac bypass surgery.\nlimitations: The clinical experiment did not directly measure intracellular cobalamin oxidation state or prove that serum B12 stores were depleted.\nexposure: Nitrous oxide/oxygen for 24 hours, during surgery only, or no nitrous oxide; marrow morphology and deoxyuridine suppression assays.\ncross_nutrient: B12-dependent folate handling connects to DNA synthesis; linked existing MTR evidence supplies the molecular context.\n[b12-amess1978] Megaloblastic haemopoiesis in patients receiving nitrous oxide (1978). https://pubmed.ncbi.nlm.nih.gov/79709/ DOI: 10.1016/s0140-6736(78)92941-0","model_system":"Prospective perioperative study in 22 patients undergoing cardiac bypass surgery.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [b12-amess1978] Megaloblastic haemopoiesis in patients receiving nitrous oxide (1978). https://pubmed.ncbi.nlm.nih.gov/79709/ DOI: 10.1016/s0140-6736(78)92941-0","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"73145023-2982-5848-aff2-8d8875d6b9c5","stable_key":"import-7fc92b9e-9cbf-556e-8719-6b5244625250","title":"Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"ad5b3a51d36e856aa7fdfd1cc23f690b094689bad87d28e1a621a54675a01c92","revision_id":"118bd616-0c13-549f-bfeb-bc439715b89c","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}