Carcinogenic polycyclic aromatic hydrocarbon‐DNA adducts and mechanism of action

  title={Carcinogenic polycyclic aromatic hydrocarbon‐DNA adducts and mechanism of action},
  author={William M. Baird and Louisa Ada Hooven and Brinda Mahadevan},
  journal={Environmental and Molecular Mutagenesis},
Polycyclic aromatic hydrocarbons (PAHs) are a class of widespread environmental carcinogens. Most of our knowledge of their mechanisms of metabolic activation to DNA‐binding “ultimate carcinogenic” metabolites has come from analysis of the DNA interaction products formed by these highly reactive intermediates. Studies of their role in forming DNA‐binding intermediates identical to those formed in vivo from the PAH itself have also allowed identification of the particular cytochrome P450 enzymes… 

Inhibition of the formation of benzo[a]pyrene adducts to DNA in A549 lung cells exposed to mixtures of polycyclic aromatic hydrocarbons.

Differential action of monohydroxylated polycyclic aromatic hydrocarbons with estrogen receptors α and β.

Although monohydroxylated PAHs appeared to have weak agonist activity to ERβ, the results showed that they can elicit a biologically active response from ERβ in human breast cancer cells and potentially interfere with ERβ signaling pathways.

Influence of the metabolic properties of human cells on the kinetic of formation of the major benzo[a]pyrene DNA adducts

The results indicate that incubation of cells with B[a]P induces almost exclusively the formation of B PDE DNA adducts on purine bases, which support the use of the stable BPDE DNAAdducts, as relevant biomarkers of exposure to B[ a]P.

Toxic effects of methylated benzo[a]pyrenes in rat liver stem-like cells.

1-MeBaP is identified as the most potent inducer of AhR activation, stable DNA adduct formation, checkpoint kinase 1 and p53 phosphorylation, and apoptosis, and effects suggest that 1-Me BaP is a potent genotoxin eliciting a typical sequence of events ascribed to carcinogenic PAHs.

Toxification of polycyclic aromatic hydrocarbons by commensal bacteria from human skin

It is shown that readily isolable skin commensals transform B[a]P into a range of highly cyto- and genotoxic metabolites that are excreted in toxicologically relevant concentrations during growth and shows that PAH metabolism of the microbiome has to be considered a potential hazard.

Polycyclic Aromatic Hydrocarbons Activate the Aryl Hydrocarbon Receptor and the Constitutive Androstane Receptor to Regulate Xenobiotic Metabolism in Human Liver Cells

Evidence is provided that beside well-known activation of AHR, some PAHs also activate CAR, followed by subsequent expression of respective target genes, and an increased PAH ring number is associated with AHR activation as well as the induction of DNA double-strand breaks, whereas smallerPAHs activated CAR but showed no DNA-damaging potential.



Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and1B1

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously distributed environmental chemicals. PAHs acquire carcinogenicity only after they have been activated by xenobiotic‐metabolizing enzymes to

Synergistic mechanisms in carcinogenesis by polycyclic aromatic hydrocarbons and by tobacco smoke: a bio-historical perspective with updates.

  • H. Rubin
  • Biology, Medicine
  • 2001
There are indications that the nicotine-derived NNK which is a specific pulmonary carcinogen in animals contributes to smoking-induced lung cancer in man and a major role for selection in carcinogenesis by cigarette smoke is indicated.

Inhibition of gap-junctional intercellular communication by environmentally occurring polycyclic aromatic hydrocarbons.

Based on the IC50 values related to the reference PAH benzo[a]pyrene, arbitrary values of inhibition equivalency factors (GJIC-IEFs) ranging from 0 (noninhibiting PAHs) to 10.0 (strongest inhibitors) are suggested, suitable for the purposes of environmental risk assessment.

Effect of a complex environmental mixture from coal tar containing polycyclic aromatic hydrocarbons (PAH) on the tumor initiation, PAH-DNA binding and metabolic activation of carcinogenic PAH in mouse epidermis.

Results are consistent with the hypothesis that two major factors determining the carcinogenic activity of PAH within a complex mixture are the persistence of certain PAH-DNA adducts as well as total adduct levels and the ability of the components present in the mixture to inhibit the activation of carcinogenic PAH by the induced CYP enzymes.

DNA reactions, mutagenic action and stealth properties of polycyclic aromatic hydrocarbon carcinogens (review).

The concept of stealth properties of potent carcinogens, i.e. their ability to damage DNA without inducing a G1 arrest, is discussed and the sequence-dependence of site-specific mutation, as well as the selectivity of hydrocarbon-DNA adduct formation are summarized.


This review summarizes recent advances in the understanding of biological mechanisms of BaP toxicity at the molecular level, and the role of metabolic intermediates in carcinogenesis, atherogenesis, and teratogenesis.

Polycyclic aromatic hydrocarbons in the diet.

Induction of cytochrome P4501A1.

  • J. Whitlock
  • Biology, Chemistry
    Annual review of pharmacology and toxicology
  • 1999
Mechanistic analyses of cytochrome P4501A1 induction provide insights into ligand-dependent mammalian gene expression, basic helix-loop-helix/Per-Arnt-Sim protein function, and dioxin action; such studies also impact public health issues concerned with molecular epidemiology, carcinogenesis, and risk assessment.

Cocarcinogenic and tumor-promoting agents in tobacco carcinogenesis.

A series of 21 tobacco smoke components and related compounds were applied to mouse skin three times weekly with a low dose of benzo[a]pyrene to assess carcinogenicity and found no direct correlation existed between tumor-promoting activity and cocarcinogenic activity.

Polycyclic aromatic hydrocarbons and cancer in man.

These new findings suggest that the current threshold limit value of 0.2 mg/m3 of benzene soluble matter (which indicates PAH exposure) is unacceptable because, after 40 years of exposure, it involves a relative risk of 1.2-1.4 for lung cancer and 2.2 for bladder cancer.