ArticleEnvironmental health perspectives2016
Synergistic and Antagonistic Mutation Responses of Human MCL-5 Cells to Mixtures of Benzo[a]pyrene and 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]pyridine: Dose-Related Variation in the Joint Effects of Common Dietary Carcinogens.
Article in Environmental health perspectives, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 27 citations in OpenAlex.
- The interactions and combined effects of benzo[iScience · 2026Review
- Checkpoint and recombination pathways independently suppress rates of spontaneous homology-directed chromosomal translocations in budding yeast.Frontiers in genetics · 2025Article
- Article
- Antagonistic Interactions between Benzo[a]pyrene and Fullerene (CNanomaterials (Basel, Switzerland) · 2019Article
- Mechanistic evidence that benzo[a]pyrene promotes an inflammatory microenvironment that drives the metastatic potential of human mammary cells.Archives of toxicology · 2018Article
- Combined effects of co-exposure to formaldehyde and acrolein mixtures on cytotoxicity and genotoxicity in vitro.Environmental science and pollution research international · 2018Article
- Ethanol potentiates the genotoxicity of the food-derived mammary carcinogen PhIP in human estrogen receptor-positive mammary cells: mechanistic support for lifestyle factors (cooked red meat and ethanol) associated with mammary cancer.Archives of toxicology · 2018Article
- A miRNA signature for an environmental heterocyclic amine defined by a multi-organ carcinogenicity bioassay in the rat.Archives of toxicology · 2017Article
- DNA damage response curtails detrimental replication stress and chromosomal instability induced by the dietary carcinogen PhIP.Nucleic acids research · 2016Article
- Using 3D MCF-7 mammary spheroids to assess the genotoxicity of mixtures of the food-derived carcinogens benzo[Toxicology research · 2016Article
- Chronic Administration of Benzo(a)pyrene Induces Memory Impairment and Anxiety-Like Behavior and Increases of NR2B DNA Methylation.PloS one · 2016Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChemical carcinogens such as benzo[a]pyrene (BaP) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) may contribute to the etiology of human diet-associated cancer. Individually, these compounds are genotoxic, but the consequences of exposure to mixtures of these chemicals have not been systematically examined.
objectivesWe determined the mutagenic response to mixtures of BaP and PhIP at concentrations relevant to human exposure (micromolar to subnanomolar).
methodsHuman MCL-5 cells (metabolically competent) were exposed to BaP or PhIP individually or in mixtures. Mutagenicity was assessed at the thymidine kinase (TK) locus, CYP1A activity was determined by ethoxyresorufin-O-deethylase (EROD) activity and qRT-PCR, and cell cycle was measured by flow cytometry.
resultsMixtures of BaP and PhIP produced dose responses different from those of the individual chemicals; we observed remarkably increased mutant frequency (MF) at lower concentrations of the mixtures (not mutagenic individually), and decreased MF at higher concentrations of the mixtures, than the calculated predicted additive MF of the individual chemicals. EROD activity and CYP1A1 mRNA levels were correlated with TK MF, supporting involvement of the CYP1A family in mutation. Moreover, a cell cycle G2/M phase block was observed at high-dose combinations, consistent with DNA damage sensing and repair.
conclusionsMixtures of these genotoxic chemicals produced mutation responses that differed from those expected for the additive effects of the individual chemicals. The increase in MF for certain combinations of chemicals at low concentrations that were not genotoxic for the individual chemicals, as well as the nonmonotonic dose response, may be important for understanding the mutagenic potential of food and the etiology of diet-associated cancers. CITATION: David R, Ebbels T, Gooderham N. 2016. Synergistic and antagonistic mutation responses of human MCL-5 cells to mixtures of benzo[a]pyrene and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine: dose-related variation in the joint effects of common dietary carcinogens. Environ Health Perspect 124:88-96; http://dx.doi.org/10.1289/ehp.1409557.
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