{"id":"9e3815ff-c680-5596-b0b6-747c5ac645cc","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-ahr-partial-antagonism","predicate":"attenuates_tcdd_induced","statement":"DIM partly inhibited TCDD-induced CYP1A1 transcription and strongly reduced the induced EROD activity in T47D cells.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e5d4a229-ae63-5d58-9640-2e18a9732270","mechanism_event_label":"Binding the same receptor can produce a weaker signal and reduce another ligand response.","subject":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"object":{"id":"95f0cce2-8f07-53f1-8cb7-3b5fb4338190","slug":"cyp1a1","display_name":"Human cytochrome P450 1A1","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"e5d4a229-ae63-5d58-9640-2e18a9732270","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-ahr-partial-antagonism-event","event_type":"biochemical_relationship","label":"Binding the same receptor can produce a weaker signal and reduce another ligand response.","description":"DIM partly inhibited TCDD-induced CYP1A1 transcription and strongly reduced the induced EROD activity in T47D cells.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"757ea2d0-1c8e-5453-a721-4a3a3443a383","slug":"ahr","display_name":"Human aryl hydrocarbon receptor / AHR","entity_type_key":"protein"},"role":"receptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e3920272-2ff4-50d1-a6f6-79998a623cf3","slug":"tcdd","display_name":"2,3,7,8-Tetrachlorodibenzo-p-dioxin / TCDD","entity_type_key":"small_molecule"},"role":"competing_stimulus","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6009bdd4-f1b5-5867-b5c3-cdf7c9645cd0","slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"95f0cce2-8f07-53f1-8cb7-3b5fb4338190","slug":"cyp1a1","display_name":"Human cytochrome P450 1A1","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/8866829.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b6df68a4c8fabdb1ec4bf4c05e25c0ac350fe1505222b1423cd2124e26c9eb7f\", \"start_char\": 0, \"end_char\": 1403, \"text_sha256\": \"b6df68a4c8fabdb1ec4bf4c05e25c0ac350fe1505222b1423cd2124e26c9eb7f\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Receptor competition, reporter and enzyme assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"DIM alone up to 31 micromolar or with TCDD","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Partial antagonism of a coadministered strong ligand is not absence of all AhR binding or a contradiction of induction in another cell type.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human T47D breast-cancer cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Binding the same receptor can produce a weaker signal and reduce another ligand response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p8866829] Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. (1996). https://pubmed.ncbi.nlm.nih.gov/8866829/ DOI: 10.1016/0006-2952(96)00060-3","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"AhR-mediated CYP1A1 response","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"4efa5233-d281-5a8f-8134-70de552834b3","evidence_kind":"source_excerpt","locator":"Lines 324-335","start_line":324,"end_line":335,"excerpt":"### dim-ahr-partial-antagonism\nDIM partly inhibited TCDD-induced CYP1A1 transcription and strongly reduced the induced EROD activity in T47D cells.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Binding the same receptor can produce a weaker signal and reduce another ligand response.\norganism: Human T47D breast-cancer cells\ntissue_or_cell_type: AhR-mediated CYP1A1 response\nexperimental_model: Receptor competition, reporter and enzyme assays\nlimitations: Partial antagonism of a coadministered strong ligand is not absence of all AhR binding or a contradiction of induction in another cell type.\nexposure: DIM alone up to 31 micromolar or with TCDD\nevidence_span: {\"source_cache\": \"artifacts/dim-research/8866829.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b6df68a4c8fabdb1ec4bf4c05e25c0ac350fe1505222b1423cd2124e26c9eb7f\", \"start_char\": 0, \"end_char\": 1403, \"text_sha256\": \"b6df68a4c8fabdb1ec4bf4c05e25c0ac350fe1505222b1423cd2124e26c9eb7f\"}\n[dim-p8866829] Indole-3-carbinol and diindolylmethane as aryl hydrocarbon (Ah) receptor agonists and antagonists in T47D human breast cancer cells. 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