CYP1A1 functions in detoxifying xenobiotics but occasionally converts compounds into potent genotoxins. CYP1A1 activates polyaromatic hydrocarbons, such as benzo[a]pyrene 7,8 dihydrodiol (BaP-DHD), rendering them genotoxic. Particular alleles of CYP1A1, such as CYP1A1 I462V have been correlated with a higher incidence of breast and lung cancer, but it is unknown whether these variants express enzymes in vivo that are more potent in generating genotoxins. We individually expressed CYP1A1 (CYP1A1.1), CYP1A1 T461N (CYP1A1.4) and I462V (CYP1A1.2) alleles in wild-type and DNA repair deficient mutant strains of Saccharomyces cerevisiae (budding yeast) and asked which yeast strains exhibited the highest levels of carcinogen-associated genotoxicity after exposure to BaP-DHD, aflatoxin B1 (AFB1), and heterocyclic aromatic amines (HAAs). We measured carcinogen-associated recombination, Rad51 foci, and carcinogen-associated toxicity in a DNA repair mutant deficient in both nucleotide excision repair and recombinational repair. CYP1A1 activity was confirmed by measuring ethoxyresorufin-O-deethylation (EROD) activities. Our data indicate that CYP1A1 I462V allele confers the least carcinogen-associated genotoxicity, compared to CYP1A1; however, results vary depending on the chemical carcinogen and the genotoxic endpoint. We speculate that the cancer-associated risk of CYP1A1 I462V may be caused by exposure to other xenobiotics.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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| Evidence ID | Analyze ID | File | Description |
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