Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Jan 16;86(3-4):103-6.
doi: 10.1016/j.lfs.2009.11.008. Epub 2009 Nov 20.

N-acetyltransferase 2 activity and folate levels

Wen Cao  1 , Diana Strnatka, Charlene A McQueen, Robert J Hunter, Robert P Erickson
Affiliations

N-acetyltransferase 2 activity and folate levels

Wen Cao et al. Life Sci. .

Abstract

Aims: To determine whether increased N-acetyltransferase (NAT) activity might have a toxic effect during development and an influence on folate levels since previous work has shown that only low levels of exogenous NAT can be achieved in constitutionally transgenic mice (Cao et al. 2005).

Main methods: A human NAT1 tet-inducible construct was used that would not be expressed until the inducer was delivered. Human NAT1 cDNA was cloned into pTRE2 and injected into mouse oocytes. Two transgenic lines were crossed to mouse line TgN(rtTahCMV)4Uh containing the CMV promoted "tet(on)". Measurements of red blood cell folate levels in inbred strains of mice were performed.

Key findings: Only low levels of human NAT1 could be achieved in kidney (highly responsive in other studies) whether the inducer, doxycycline, was given by gavage or in drinking water. An inverse correlation of folate levels with Nat2 enzyme activity was found.

Significance: Since increasing NAT1 activity decreases folate in at least one tissue, the detrimental effect of expression of human NAT1 in combination with endogenous mouse Nat2 may be a consequence of increased catabolism of folate.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

References

    1. Cao W, Chau B, Hunter R, Strnatka D, McQueen CA, Erickson RP. Only low levels of exogenous N-acetyltransferase can be achieved in transgenic mice. Pharmacogenomics J. 2005;5:255–261. - PubMed
    1. Erickson RP, McQueen CA, Chau B, Gokhale V, Uchiyama M, Toyoda A, Ejima F, Maho Sakaki Y, Gondo Y. An N-ethyl-N-nitrosourea-induced mutation in N-acetyltransferase 1 in mice. Biochem Biophys Res Commun. 208a;370:285–288. - PubMed
    1. Erickson RP, Cao W, Acuna DK, Strnatka DW, Hunter RJ, Chau BT, Wakefield LV, Sim E, McQueen CA. Confirmation of the role of N-acetyltransferase 2 in teratogen-induced cleft palate using transgenics and knockouts. Molecular Reproduction and Development. 2008b;75:1071–1076. - PubMed
    1. Estrada-Rodgers L, Levy GN, Weber WW. Substrate selectivity of mouse N-acetyltransferases 1, 2 and 3 expressed in COS-1 cell. Drug Metab Dispo. 1998;26:502–505. - PubMed
    1. Fretland AJ, Doll MA, Gray K, Feng Y, Hein DW. Cloning, sequencing, andd recombinant expression of NAT1, NAT2, and NAT3 derived from the C3H/HeJ (rapid) and A/HeJ (slow) acetylator inbred mouse: functional characterization of the activation and deactivation of aromatic amine carcinogens. Toxic and Appl Pharm. 1997;142:360–366. - PubMed

Publication types

MeSH terms