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

@article{Shimada2004MetabolicAO,
  title={Metabolic activation of polycyclic aromatic hydrocarbons to carcinogens by cytochromes P450 1A1 and1B1},
  author={Tsutomu Shimada and Yoshiaki Fujii‐Kuriyama},
  journal={Cancer Science},
  year={2004},
  volume={95}
}
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitously distributed environmental chemicals. PAHs acquire carcinogenicity only after they have been activated by xenobiotic‐metabolizing enzymes to highly reactive metabolites capable of attacking cellular DNA. Cytochrome P450 (CYP) enzymes are central to the metabolic activation of these PAHs to epoxide intermediates, which are converted with the aid of epoxide hydrolase to the ultimate carcinogens, diol‐epoxides. Historically, CYP1A1 was… 

Xenobiotic-metabolizing enzymes involved in activation and detoxification of carcinogenic polycyclic aromatic hydrocarbons.

  • T. Shimada
  • Biology, Chemistry
    Drug metabolism and pharmacokinetics
  • 2006
TLDR
Inter-individual differences exist in levels of expression and catalytic activities of a variety of enzymes that activate and/or detoxify PAHs in various organs of humans and these phenomena are thought to be critical in understanding the basis of individual differences in response toPAHs.

Inhibition of Carcinogen-Activating Cytochrome P450 Enzymes by Xenobiotic Chemicals in Relation to Antimutagenicity and Anticarcinogenicity

  • T. Shimada
  • Chemistry, Biology
    Toxicological research
  • 2017
TLDR
Recent progress is described on the nature of inhibitors of human CYP1 and CYP2A enzymes that have been shown to activate carcinogenic PAHs and tobacco-related nitrosamines, respectively, in humans.

Exposure to an Environmental Mixture of Polycyclic Aromatic Hydrocarbons Induces Hepatic Cytochrome P450 Enzymes in Mice.

TLDR
This study demonstrates exposure to PAHs found at superfund sites induces enzymes in dose- and time-dependent patterns in mice, and accounting for specific changes in enzyme profiles, relative rates of PAH bioactivation and detoxification, and resulting risk will help translate internal dosimetry of animal models to humans and improve risk assessments ofPAHs at super fund sites.

Carcinogenic polycyclic aromatic hydrocarbons : Theoretical, molecular, in vitro and cellular characterization of biotransformation and DNA damage

TLDR
The results showed that the spatial orientation of the hydroxyl groups are important determinants for the catalytic efficiency and thus responsible for the observed difference in catalytic activity, and an increase in GST activity was concomitant with a decrease in DNA adduct formation.

Carcinogenic polycyclic aromatic hydrocarbon‐DNA adducts and mechanism of action

TLDR
PAHs may also act through a promotional mechanism in addition to serving as tumor initiators, and cause changes in cellular gap‐junction communication similar to those caused by the tumor promoter 12‐O‐tetradecanoylphorbol‐13‐acetate.

Role of Metabolic Enzymes P450 (CYP) on Activating Procarcinogen and their Polymorphisms on the Risk of Cancers.

TLDR
CYP1A1, CYP1A2, CYp1B1, CyP2A6, and CYP2E1 are responsible for most of the procarcinogens activation, and their gene polymorphisms are associated with the risk of cancers.

Interaction of polycyclic aromatic hydrocarbons with human cytochrome P450 1B1 in inhibiting catalytic activity.

TLDR
The results suggest that P450 1B1 interacts with synthetic polycyclic aromatic acetylenes and PAHs in different ways, depending on the chemicals, and that these differences in interactions may explain how these chemicals inhibit P450 activities by different mechanisms.

Understanding the effects of dietary chemopreventive agents on metabolism and mutagenicity of polycyclic aromatic hydrocarbons by human cytochrome p450 and human glutathione S -transferase enzymes

TLDR
Based on data from the enzyme inhibition assay, it is hypothesized inhibition of BPD metabolism by resveratrol and therefore, protect against cytotoxicity and mutagenicity of B[a]P or BPD.

Cancer Activation and Polymorphisms of Human Cytochrome P450 1B1

TLDR
It is necessary to understand the relationship between metabolic activation of such substances and P450 1B1 polymorphisms in order to develop rational strategies for the prevention of its toxic effect on human health.
...

References

SHOWING 1-10 OF 64 REFERENCES

Metabolic activation of polycyclic aromatic hydrocarbons and other procarcinogens by cytochromes P450 1A1 and P450 1B1 allelic variants and other human cytochromes P450 in Salmonella typhimurium NM2009.

TLDR
There were good correlations between activities of procarcinogen activation by CYP1A1 preparations expressed in E. coli and T. ni cells, and the resultant DNA damage caused by the reactive metabolites was detected by measuring expression of umu gene in the cells.

Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1.

TLDR
The selectivity of this enzyme in the activation of a variety of environmental carcinogens and mutagens in Salmonella typhimurium TA1535/pSK1002 or NM2009 tester strains was examined using the SOS response as an end point of DNA damage.

Metabolic activation of dibenzo[a,l]pyrene by human cytochrome P450 1A1 and P450 1B1 expressed in V79 Chinese hamster cells.

TLDR
Synthesis and spectroscopic characterization of the trans-DB[a,l]P-8,9-diol and its individual enantiomers have been achieved and it was revealed that this compound is converted by human P450s 1A1 and 1B1 to several diol phenols and bis-Diols.

Benzo[a]pyrene-induced toxicity: paradoxical protection in Cyp1a1(-/-) knockout mice having increased hepatic BaP-DNA adduct levels.

TLDR
The results suggest that absence of the CYP1A1 enzyme protects the intact animal from BaP-mediated liver toxicity and death, by decreasing the formation of large amounts of toxic metabolites, whereas much slower metabolic clearance of BaP in Cyp1a1(-/-) mice leads to greater formation ofBaP-DNA adducts.

Arylhydrocarbon receptor-dependent induction of liver and lung cytochromes P450 1A1, 1A2, and 1B1 by polycyclic aromatic hydrocarbons and polychlorinated biphenyls in genetically engineered C57BL/6J mice.

TLDR
The results suggest that carcinogenicity potencies of PAHs may relate to the Potencies of these compounds to induce CYP1A1 and 1B1 through AhR-dependent manner and that these induced P450s participate in the activation of B[a]P and related carcinogens causing initiation of cancers in mice.

Biological Oxidations and P450 Reactions

TLDR
It is established that the CYP1B1 cDNA indeed encodes the P450 responsible for polycyclic aromatic hydrocarbon (PAH) metabolism from C3H10T1/2 cells, which is an important contributor to activation of PAHs, particularly in extra hepatic tissues that are susceptible to cancer.

Biological oxidations and P450 reactions. Recombinant mouse CYP1B1 expressed in Escherichia coli exhibits selective binding by polycyclic hydrocarbons and metabolism which parallels C3H10T1/2 cell microsomes, but differs from human recombinant CYP1B1.

TLDR
It is established that the CYP1B1 cDNA indeed encodes the P450 responsible for polycyclic aromatic hydrocarbon (PAH) metabolism from C3H10T1/2 cells, which is an important contributor to activation of PAHs, particularly in extra hepatic tissues that are susceptible to cancer.

Inhibition of human cytochrome P450-catalyzed oxidations of xenobiotics and procarcinogens by synthetic organoselenium compounds.

TLDR
The three XSCs were found to be very potent inhibitors of metabolic activation of 3-amino-1,4-dimethyl-5H-pyrido, 2-Amino-3,5-dimethylimidazo[4,3-b]indole, and 2-AMinoanthracene, catalyzed by CYP1A1, 1A2, and 1B1, respectively.
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