{"id":"923a2e70-c93a-5b07-b866-f055d4ea7d1a","stable_key":"44eaeae5-557a-552b-8998-884f30462e2a:sulforaphane-cyp3a4-transcription","predicate":"reduced_expression_of","statement":"Sulforaphane strongly reduced CYP3A4 mRNA in primary human hepatocytes without inducing GSTM1 or GSTT1 expression.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"d0cf6d29-7572-5b40-9aae-ee7c559bb34d","mechanism_event_label":"Suppressed activation machinery, rather than increased GST expression, accompanied the response.","subject":{"id":"67e70215-70c4-546a-84b4-0819fac0b326","slug":"sulforaphane","display_name":"Sulforaphane / SFN, stereochemistry specified per study","entity_type_key":"small_molecule"},"object":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"d0cf6d29-7572-5b40-9aae-ee7c559bb34d","stable_key":"44eaeae5-557a-552b-8998-884f30462e2a:sulforaphane-cyp3a4-transcription-event","event_type":"biochemical_relationship","label":"Suppressed activation machinery, rather than increased GST expression, accompanied the response.","description":"Sulforaphane strongly reduced CYP3A4 mRNA in primary human hepatocytes without inducing GSTM1 or GSTT1 expression.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b6266d89-a23f-5a9f-92e4-67bec1f74236","slug":"gstm1","display_name":"Human glutathione S-transferase M1","entity_type_key":"protein"},"role":"genotype_modifier","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"67e70215-70c4-546a-84b4-0819fac0b326","slug":"sulforaphane","display_name":"Sulforaphane / SFN, stereochemistry specified per study","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/sulforaphane-research/20442190.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"130e0a3ab9cbabd496a64344ae8bfb9f98cccbf7521a64ec807f14b2259ceb69\", \"start_char\": 0, \"end_char\": 1705, \"text_sha256\": \"130e0a3ab9cbabd496a64344ae8bfb9f98cccbf7521a64ec807f14b2259ceb69\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Primary human hepatocyte pretreatment and genotyping","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Sulforaphane 10 or 50 micromolar for 48 hours before aflatoxin B1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Culture exposures are not ordinary plasma exposures; reduced CYP3A4 mRNA does not establish the direction of clinical drug interactions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Sulforaphane research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"sulforaphane","display_name":"Sulforaphane / SFN, stereochemistry specified per study","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human hepatocyte cultures","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Suppressed activation machinery, rather than increased GST expression, accompanied the response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[sulforaphane-p20442190] Sulforaphane- and phenethyl isothiocyanate-induced inhibition of aflatoxin B1-mediated genotoxicity in human hepatocytes: role of GSTM1 genotype and CYP3A4 gene expression. (2010). https://pubmed.ncbi.nlm.nih.gov/20442190/ DOI: 10.1093/toxsci/kfq135","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Aflatoxin activation and DNA damage","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ec3973ec-14b8-5d60-b2cf-e1317174f405","evidence_kind":"source_excerpt","locator":"Lines 1230-1241","start_line":1230,"end_line":1241,"excerpt":"### sulforaphane-cyp3a4-transcription\nSulforaphane strongly reduced CYP3A4 mRNA in primary human hepatocytes without inducing GSTM1 or GSTT1 expression.\nCondition category: normal\nnutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Suppressed activation machinery, rather than increased GST expression, accompanied the response.\norganism: Human hepatocyte cultures\ntissue_or_cell_type: Aflatoxin activation and DNA damage\nexperimental_model: Primary human hepatocyte pretreatment and genotyping\nlimitations: Culture exposures are not ordinary plasma exposures; reduced CYP3A4 mRNA does not establish the direction of clinical drug interactions.\nexposure: Sulforaphane 10 or 50 micromolar for 48 hours before aflatoxin B1\nevidence_span: {\"source_cache\": \"artifacts/sulforaphane-research/20442190.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"130e0a3ab9cbabd496a64344ae8bfb9f98cccbf7521a64ec807f14b2259ceb69\", \"start_char\": 0, \"end_char\": 1705, \"text_sha256\": \"130e0a3ab9cbabd496a64344ae8bfb9f98cccbf7521a64ec807f14b2259ceb69\"}\n[sulforaphane-p20442190] Sulforaphane- and phenethyl isothiocyanate-induced inhibition of aflatoxin B1-mediated genotoxicity in human hepatocytes: role of GSTM1 genotype and CYP3A4 gene expression. (2010). https://pubmed.ncbi.nlm.nih.gov/20442190/ DOI: 10.1093/toxsci/kfq135","model_system":"Primary human hepatocyte pretreatment and genotyping","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [sulforaphane-p20442190] Sulforaphane- and phenethyl isothiocyanate-induced inhibition of aflatoxin B1-mediated genotoxicity in human hepatocytes: role of GSTM1 genotype and CYP3A4 gene expression. (2010). https://pubmed.ncbi.nlm.nih.gov/20442190/ DOI: 10.1093/toxsci/kfq135","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"a4bafbf7-f117-53c9-a6d7-8fb25e4aca72","stable_key":"import-44eaeae5-557a-552b-8998-884f30462e2a","title":"Sulforaphane: formation, electrophile sensing and nutrient connections (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":"f355c492a6c35673d8260b1328667fe206e5315b9fcaa5aeff53d80373c7ef97","revision_id":"f2c47d71-34cd-5160-8e92-fe196b576707","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}