• Corpus ID: 13508470

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

@article{Shimada1996ActivationOC,
  title={Activation of chemically diverse procarcinogens by human cytochrome P-450 1B1.},
  author={Tsutomu Shimada and Carrie L. Hayes and Hiroshi Yamazaki and Shantu Amin and Stephen S. Hecht and F. Peter Guengerich and Thomas R. Sutter},
  journal={Cancer research},
  year={1996},
  volume={56 13},
  pages={
          2979-84
        }
}
A human cytochrome P-450 (P450) 1B1 cDNA was expressed in Saccharomyces cerevisiae and the microsomes containing P450 1B1 were used to examine 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, using the SOS response as an end point of DNA damage. We also determined and compared these activities of P450 1B1 with those catalyzed by recombinant human P450s 1A1 and 1A2, which… 
View on PubMed
cancerres.aacrjournals.org
832 Citations
Highly Influential Citations
44
Background Citations
311
Methods Citations
18
Results Citations
5

Figures and Tables from this paper

832 Citations

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.

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.

Procarcinogens by Cytochromes P 450 1 a 1 and P 450 1 B 1 Allelic Variants and Other Human Cytochromes P 450 in Salmonella Typhimurium Nm 2009

A variety of polycyclic aromatic hydrocarbons and their dihydrodiol derivatives, arylamines, heterocyclic amines, and nitroarenes, were incubated with cDNA-based recombinant systems expressing different forms of human cytochrome P450 (P450 or CYP) and NADPH-P450 reductase and the resultant DNA damage caused by the reactive metabolites was detected by measuring expression of umu gene in the cells.

Oxidation of xenobiotics by recombinant human cytochrome P450 1B1.

CYP1B1 has catalytic activities overlapping CYP1A1 and CYP 1A2 with respect to the oxidation of drugs and model P450 substrates, although the relative catalytic roles in these three P450 enzymes differ depending upon the substrates examined.

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

  • T. Shimada
  • Chemistry, Biology
    Toxicological research
  • 2017
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.

Recombinant human cytochrome P450 1B1 expression in Escherichia coli.

The ability of human P450 1B1 to activate several heterocyclic amines and polycyclic hydrocarbon dihydrodiols was confirmed with reconstituted P450 2B1 and the P4501B1 membranes in which NADPH-P450 reductase was coexpressed.

Recombinant human P450 forms 1A1, 1A2, and 1B1 catalyze the bioactivation of heterocyclic amine mutagens in Escherichia coli lacZ strains

Three recombinant human P450 enzymes, forms 1A1, 1A2, and 1B1, were coexpressed with NADPH–cytochrome P450 reductase in an E. coli lacZ strain suitable for detection of the mutagenicity of…

Metabolic activation of heterocyclic amines and other procarcinogens in Salmonella typhimurium umu tester strains expressing human cytochrome P4501A1, 1A2, 1B1, 2C9, 2D6, 2E1, and 3A4 and human NADPH-P450 reductase and bacterial O-acetyltransferase.

Biological Oxidations and P450 Reactions

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.

Cytochrome P450 1B1: a target for inhibition in anticarcinogenesis strategies.

Inhibition of carcinogen-bioactivating cytochrome P450 1 isoforms by amiloride derivatives.

...

References

SHOWING 1-10 OF 90 REFERENCES

Activation of procarcinogens by human cytochrome P450 enzymes expressed in Escherichia coli. Simplified bacterial systems for genotoxicity assays.

Bacterial assays were used to examine the activation of 14 known procarcinogens by cytochrome P450 (P450) enzymes and the patterns of activation were consistent with the literature developed using human liver microsomes, purified liver P450s and other approaches.

Roles of individual human cytochrome P-450 enzymes in the bioactivation of benzo(a)pyrene, 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene, and other dihydrodiol derivatives of polycyclic aromatic hydrocarbons.

The roles of the human P-450 enzymes differ from the rodent orthologs in the paradigm for bioactivation of polycyclic hydrocarbons; further, flavones appear to have opposing effects on diol formation and further epoxidation in both human liver and lung.

Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines.

Estimation of caffeine 3-demethylation activity in humans may be useful in the characterization of arylamine N-oxidation phenotypes and in the assessment of whether or not the hepatic levels of cytochrome P-450PA, as affected by environmental or genetic factors, contribute to interindividual differences in susceptibility to arieslamine-induced cancers.

Characterization of a novel cytochrome P450 from the transformable cell line, C3H/10T1/2.

The distinct metabolite profiles, antibody inhibition data and lack of immunoreactivity all indicate that PAH metabolism in 10T1/2 cells is catalyzed by a form of P450 distinct from P450IA1, which is predominantly regulated by a mechanism other than the Ah receptor.

Roles of cytochrome P-450 enzymes in chemical carcinogenesis and cancer chemotherapy.

Studies involving the metabolism of chemical carcinogens were important in the discovery and initial characterization of the cytochrome P-450 enzyme system. The Millers and their associates…

Characterization of human lung microsomal cytochrome P-450 1A1 and its role in the oxidation of chemical carcinogens.

This work clearly shows that human lung microsomes contain at least two major P- 450 enzymes; human P-450 1A1 is present in lungs and can actually catalyze the activation of environmental procarcinogens, including polycyclic aromatic hydrocarbons.

Mouse cytochrome P-450EF, representative of a new 1B subfamily of cytochrome P-450s. Cloning, sequence determination, and tissue expression.

Hybridization of mRNA and immunoblot analyses of microsomes both demonstrated beta-naphthoflavone (beta-NF) inducibility of Cyp1b-1 expression in C3H mouse lung, liver, and uterus although at lower levels relative to Cyp1a-1.

Human dioxin-inducible cytochrome P1-450: complementary DNA and amino acid sequence.

Whereas the mouse TCDD-inducible P-450 gene subfamily has two members (P1-450 and P3-450), the human T CDD-Inducible gene sub family appears to have only one gene (P 1-450).

Expression of modified human cytochrome P450 1A1 in Escherichia coli: effects of 5' substitution, stabilization, purification, spectral characterization, and catalytic properties.

The successful expression and purification of human P450 1A1 should increase the availability of this enzyme and the generation of antibodies for further biochemical and other biological studies.

Activation of Amino-α-carboline, 2-Amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine, and a Copper Phthalocyanine Cellulose Extract of Cigarette Smoke Condensate by Cytochrome P-450 Enzymes in Rat and Human Liver Microsomes

Cigarette smoke condensate strongly inhibited the activation of several potent procarcinogens by human liver microsomes, but was not so inhibitory of the activation reactions catalyzed by P-450 3A4 and of P- 450 2D6-catalyzed bufuralol 1′-hydroxylation.
...