Reduced 4-aminobiphenyl-induced liver tumorigenicity but not DNA damage in arylamine N-acetyltransferase null mice.

Abstract

The aromatic amine 4-aminobiphenyl (ABP) is a liver procarcinogen in mice, requiring enzymatic bioactivation to exert its tumorigenic effect. To assess the role of arylamine N-acetyltransferase (NAT)-dependent acetylation capacity in the risk for ABP-induced liver tumors, we compared 1-year liver tumor incidence following the postnatal exposure of wild-type and NAT-deficient Nat1/2(-/-) mice to ABP. At an ABP exposure of 1200 nmol, male Nat1/2(-/-) mice had a liver tumor incidence of 36% compared to 69% in wild-type males, and at 600 nmol there was a complete absence of tumors compared to 60% in wild-type mice. Only one female wild-type mouse had a tumor using this exposure protocol. However, levels of N-deoxyguanosin-8-yl-ABP-DNA adducts did not correlate with either the strain or sex differences in tumor incidence. These results suggest that female sex and NAT deficiency reduce risk for ABP-induced liver tumors, but by mechanisms unrelated to differences in DNA-damaging events.

• Authors: Kim S Sugamori, Debbie Brenneman, Otto Sanchez, Mark A Doll, David W Hein, William M Pierce Jr, Denis M Grant
• Journal: Cancer letters (Cancer Lett) Vol. 318 Issue 2 Pg. 206-13 (May 28 2012) ISSN: 1872-7980 [Electronic] Ireland
• PMID: 22193722 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Aminobiphenyl Compounds
• Carcinogens
• 4-biphenylamine
• Arylamine N-Acetyltransferase

Topics

• Aminobiphenyl Compounds (toxicity)
• Animals
• Arylamine N-Acetyltransferase (genetics, metabolism)
• Carcinogens (toxicity)
• DNA Damage
• Female
• Liver Neoplasms, Experimental (chemically induced, enzymology, genetics)
• Male
• Mice
• Mice, Knockout