Human cytochrome P450 1A1

evidence_span

{"source_cache": "artifacts/dim-research/8591723.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e", "start_char": 0, "end_char": 1460, "text_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e"}

experimental_model

Human microsomes and individually expressed enzymes

exposure

Enzyme-specific inhibitors and radiolabeled substrate

limitations

CYP3A is identified at subfamily level, without an exclusive isoform assignment. Multiple CYP pathways contribute; no DIM coadministration or clinically measured DIM effect.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human CYP systems

plain_language

A substrate list alone omits other routes that can limit a single-enzyme interaction.

primary_references

[dim-p8591723] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/8591723/ DOI: 10.1016/s0090-9556(25)06820-5

tissue_or_cell_type

Ondansetron oxidation

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 935–946

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human microsomes and individually expressed enzymes · source_derived_draft · unverified_draft

### dim-ondansetron-cyp1a1 CYP1A1 contributed to ondansetron metabolism in the studied human systems. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: A substrate list alone omits other routes that can limit a single-enzyme interaction. organism: Human CYP systems tissue_or_cell_type: Ondansetron oxidation experimental_model: Human microsomes and individually expressed enzymes limitations: CYP3A is identified at subfamily level, without an exclusive isoform assignment. Multiple CYP pathways contribute; no DIM coadministration or clinically measured DIM effect. exposure: Enzyme-specific inhibitors and radiolabeled substrate evidence_span: {"source_cache": "artifacts/dim-research/8591723.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e", "start_char": 0, "end_char": 1460, "text_sha256": "04a615c551d95089eb1a966d88d8be011687d658f383e81af5b651845427b66e"} [dim-p8591723] Multiple forms of cytochrome P450 are involved in the metabolism of ondansetron in humans. (1995). https://pubmed.ncbi.nlm.nih.gov/8591723/ DOI: 10.1016/s0090-9556(25)06820-5

evidence_span

{"source_cache": "artifacts/melatonin-research/15616152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2", "start_char": 0, "end_char": 1733, "text_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2"}

experimental_model

Recombinant P450 screen and mouse brain comparisons

exposure

Eleven P450 isozymes; NADPH-dependent 6-hydroxylation/O-demethylation

limitations

Catalytic capacity in an enzyme assay is not whole-body contribution. CYP1B1 is an extrahepatic route; human proteins are not substituted for mouse knockout identity.

nutrient_topic

Melatonin research collection; topical membership is not evidence of a direct dietary effect. · Melatonin

organism

Human recombinant enzymes; separate mouse knockout experiment

plain_language

Melatonin has multiple metabolic routes whose importance depends on enzyme and tissue.

primary_references

[melatonin-p15616152] Metabolism of melatonin by human cytochromes p450. (2005). https://pubmed.ncbi.nlm.nih.gov/15616152/ DOI: 10.1124/dmd.104.002410

tissue_or_cell_type

Oxidative melatonin metabolism

Melatonin: synthesis, receptors, circadian timing and nutrient interactions (2026-09-17) · lines 565–576

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant P450 screen and mouse brain comparisons · source_derived_draft · unverified_draft

### melatonin-cyp-1a1-hydroxylation Recombinant human CYP1A1 catalyzed melatonin 6-hydroxylation. Condition category: normal nutrient_topic: Melatonin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Melatonin has multiple metabolic routes whose importance depends on enzyme and tissue. organism: Human recombinant enzymes; separate mouse knockout experiment tissue_or_cell_type: Oxidative melatonin metabolism experimental_model: Recombinant P450 screen and mouse brain comparisons limitations: Catalytic capacity in an enzyme assay is not whole-body contribution. CYP1B1 is an extrahepatic route; human proteins are not substituted for mouse knockout identity. exposure: Eleven P450 isozymes; NADPH-dependent 6-hydroxylation/O-demethylation evidence_span: {"source_cache": "artifacts/melatonin-research/15616152.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2", "start_char": 0, "end_char": 1733, "text_sha256": "482334074e10503323360f236e00b5b837c5b082a7cda4df000a23d491bff8a2"} [melatonin-p15616152] Metabolism of melatonin by human cytochromes p450. (2005). https://pubmed.ncbi.nlm.nih.gov/15616152/ DOI: 10.1124/dmd.104.002410

evidence_span

{"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"}

experimental_model

Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments

exposure

CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments

limitations

Relative contributions depend on species and tissue; this is not a clinical drug-interaction study.

nutrient_topic

Coumarin research collection; topical membership is not evidence of a direct dietary effect. · Coumarin

organism

Human, rat and mouse; each claim specifies enzyme origin

plain_language

CYP1A1 can route coumarin toward a reactive intermediate.

primary_references

[coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

tissue_or_cell_type

Liver and lung microsomes

Coumarin: metabolism, signaling and nutrient connections (2026-09-17) · lines 215–226

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments · source_derived_draft · unverified_draft

### coumarin-1a1-epoxide Recombinant human CYP1A enzymes catalyzed coumarin epoxidation; CYP1A1 was among the tested human forms. Condition category: normal nutrient_topic: Coumarin research collection; topical membership is not evidence of a direct dietary effect. plain_language: CYP1A1 can route coumarin toward a reactive intermediate. organism: Human, rat and mouse; each claim specifies enzyme origin tissue_or_cell_type: Liver and lung microsomes experimental_model: Recombinant CYP enzymes, immunoinhibition and mouse lung inhibitor experiments limitations: Relative contributions depend on species and tissue; this is not a clinical drug-interaction study. exposure: CYP1A/2E antibody inhibition and 5-phenyl-pentyne lung experiments evidence_span: {"source_cache": "artifacts/coumarin-research/11950775.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861", "start_char": 0, "end_char": 1158, "text_sha256": "98a03fafa68ef4d55593a3b725af646175a11b42ce02b1dfe02be84ff49d4861"} [coumarin-p11950775] Identification of the cytochromes P450 that catalyze coumarin 3,4-epoxidation and 3-hydroxylation. (2002). https://pubmed.ncbi.nlm.nih.gov/11950775/ DOI: 10.1124/dmd.30.5.483

evidence_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"}

experimental_model

Receptor competition, reporter and enzyme assays

exposure

DIM alone up to 31 micromolar or with TCDD

limitations

Partial antagonism of a coadministered strong ligand is not absence of all AhR binding or a contradiction of induction in another cell type.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human T47D breast-cancer cells

plain_language

Binding the same receptor can produce a weaker signal and reduce another ligand response.

primary_references

[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

tissue_or_cell_type

AhR-mediated CYP1A1 response

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 324–335

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor competition, reporter and enzyme assays · source_derived_draft · unverified_draft

### dim-ahr-partial-antagonism DIM partly inhibited TCDD-induced CYP1A1 transcription and strongly reduced the induced EROD activity in T47D cells. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Binding the same receptor can produce a weaker signal and reduce another ligand response. organism: Human T47D breast-cancer cells tissue_or_cell_type: AhR-mediated CYP1A1 response experimental_model: Receptor competition, reporter and enzyme assays limitations: Partial antagonism of a coadministered strong ligand is not absence of all AhR binding or a contradiction of induction in another cell type. exposure: DIM alone up to 31 micromolar or with TCDD evidence_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"} [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

evidence_span

{"source_cache": "artifacts/dim-research/19770484.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba", "start_char": 0, "end_char": 1446, "text_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba"}

experimental_model

Pretreatment versus cotreatment, adduct and recombinant-enzyme assays

exposure

DIM pretreatment for 48 hours; direct catalytic assays separately

limitations

Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Primary human hepatocytes and human enzyme preparations

plain_language

Direct enzyme inhibition can oppose a slower increase in enzyme production.

primary_references

[dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206

tissue_or_cell_type

Aflatoxin metabolism and CYP catalytic activity

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 428–439

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pretreatment versus cotreatment, adduct and recombinant-enzyme assays · source_derived_draft · unverified_draft

### dim-cyp1a1-direct-inhibition DIM directly inhibited CYP1A1 catalytic activity in the tested enzyme assay. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Direct enzyme inhibition can oppose a slower increase in enzyme production. organism: Primary human hepatocytes and human enzyme preparations tissue_or_cell_type: Aflatoxin metabolism and CYP catalytic activity experimental_model: Pretreatment versus cotreatment, adduct and recombinant-enzyme assays limitations: Induction over time and direct inhibition are distinct mechanisms. Aflatoxin assay effects do not establish human cancer incidence or net disposition of unrelated drugs. exposure: DIM pretreatment for 48 hours; direct catalytic assays separately evidence_span: {"source_cache": "artifacts/dim-research/19770484.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba", "start_char": 0, "end_char": 1446, "text_sha256": "b5956f74860b0cd89114dab4179908bae1a59aab65220ac0421f4c5365bed6ba"} [dim-p19770484] Modulation of aflatoxin B1-mediated genotoxicity in primary cultures of human hepatocytes by diindolylmethane, curcumin, and xanthohumols. (2009). https://pubmed.ncbi.nlm.nih.gov/19770484/ DOI: 10.1093/toxsci/kfp206

evidence_span

{"source_cache": "artifacts/dim-research/15672752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63", "start_char": 0, "end_char": 1560, "text_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63"}

experimental_model

Quantitative gene expression and protein assessment

exposure

DIM 10-50 micromolar

limitations

Cell-culture concentrations; fold mRNA induction is not the fold change in drug clearance in people.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Primary human hepatocytes

plain_language

The cell increases the amount of one drug-processing enzyme.

primary_references

[dim-p15672752] Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. (2004). https://pubmed.ncbi.nlm.nih.gov/15672752/ DOI: 10.1080/00498250412331285481

tissue_or_cell_type

CYP and phase-II enzyme expression

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 376–387

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Quantitative gene expression and protein assessment · source_derived_draft · unverified_draft

### dim-hepatocyte-cyp1a1 DIM increased CYP1A1 mRNA dose-dependently, with induction also reflected in protein measurements. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell increases the amount of one drug-processing enzyme. organism: Primary human hepatocytes tissue_or_cell_type: CYP and phase-II enzyme expression experimental_model: Quantitative gene expression and protein assessment limitations: Cell-culture concentrations; fold mRNA induction is not the fold change in drug clearance in people. exposure: DIM 10-50 micromolar evidence_span: {"source_cache": "artifacts/dim-research/15672752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63", "start_char": 0, "end_char": 1560, "text_sha256": "ccf97f305e0f4d5b98b172cef3a0875729e44b8f65420d87a6d725ec7207ca63"} [dim-p15672752] Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. (2004). https://pubmed.ncbi.nlm.nih.gov/15672752/ DOI: 10.1080/00498250412331285481

evidence_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"}

experimental_model

Receptor competition, reporter and enzyme assays

exposure

DIM alone up to 31 micromolar or with TCDD

limitations

Partial antagonism of a coadministered strong ligand is not absence of all AhR binding or a contradiction of induction in another cell type.

nutrient_topic

Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM

organism

Human T47D breast-cancer cells

plain_language

The induction result is not universal across cell types and exposures.

primary_references

[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

tissue_or_cell_type

AhR-mediated CYP1A1 response

Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 337–348

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor competition, reporter and enzyme assays · source_derived_draft · unverified_draft

### dim-t47d-induction-null DIM alone did not significantly induce CYP1A1 mRNA or EROD activity at concentrations up to 31 micromolar in this T47D system. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The induction result is not universal across cell types and exposures. organism: Human T47D breast-cancer cells tissue_or_cell_type: AhR-mediated CYP1A1 response experimental_model: Receptor competition, reporter and enzyme assays limitations: Partial antagonism of a coadministered strong ligand is not absence of all AhR binding or a contradiction of induction in another cell type. exposure: DIM alone up to 31 micromolar or with TCDD evidence_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"} [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