Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Prostate-specific human N-acetyltransferase 2 (NAT2) expression in the mouse.

M A Leff1, P N Epstein, M A Doll

  • 1Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville Kentucky, USA.

The Journal of Pharmacology and Experimental Therapeutics
|June 25, 1999
PubMed
Summary

Prostate-specific expression of human NAT2 in mice did not increase susceptibility to PhIP-induced prostate cancer. This suggests N-acetyltransferase 2 may not be critical for heterocyclic amine carcinogen activation in the prostate.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Impaired Albumin Uptake and Processing Promote Albuminuria in OVE26 Diabetic Mice.

Journal of diabetes research·2016
Same author

GSTM1 null and NAT2 slow acetylation genotypes, smoking intensity and bladder cancer risk: results from the New England bladder cancer study and NAT2 meta-analysis.

Carcinogenesis·2010
Same author

Acetyl CoA:arylamine N-acetyltransferase activity in rat hepatocytes cultured on different extracellular matrices.

Toxicology in vitro : an international journal published in association with BIBRA·2010
Same author

Para-phenylenediamine and allergic sensitization: risk modification by N-acetyltransferase 1 and 2 genotypes.

The British journal of dermatology·2009
Same author

Impaired baroreflex control of renal sympathetic nerve activity in type 1 diabetic mice (OVE26).

Neuroscience·2009
Same author

Role of human CYP1A1 and NAT2 in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced mutagenicity and DNA adducts.

Xenobiotica; the fate of foreign compounds in biological systems·2009

Area of Science:

  • Biochemistry
  • Toxicology
  • Genetics

Background:

  • 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a dietary and smoke-derived heterocyclic amine that causes prostate tumors in rats.
  • PhIP bioactivation involves cytochrome P-450 enzymes and conjugation enzymes like N-acetyltransferases (NAT1 and NAT2).

Purpose of the Study:

  • To investigate the role of human N-acetyltransferase 2 (NAT2) in PhIP-induced prostate cancer by creating a transgenic mouse model with prostate-specific NAT2 expression.

Main Methods:

  • Constructed transgenic mice expressing human NAT2 in the prostate.
  • Assayed NAT1 and NAT2 specific N-acetyltransferase activities in various tissues of transgenic and control mice.
  • Measured PhIP-DNA adduct levels in the prostate of mice administered PhIP.

Related Experiment Videos

Main Results:

  • Human NAT2 activity was significantly higher (15-fold) in the prostates of transgenic mice compared to controls, with no differences in other tissues.
  • No significant differences in PhIP-DNA adduct levels were observed between transgenic and control mice.
  • Prostate cytosols showed no difference in catalyzing key acetylation reactions involving PhIP metabolites.

Conclusions:

  • Transgenic expression of human NAT2 in the mouse prostate does not enhance susceptibility to PhIP-induced prostate cancer.
  • The findings do not support a critical role for NAT2 in the bioactivation of heterocyclic amine carcinogens in the prostate.
  • The lack of effect might be due to the level of NAT2 overexpression or the presence of endogenous mouse enzymes.