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

Cancer Lett. 2012 May 28;318(2):206-13. doi: 10.1016/j.canlet.2011.12.022. Epub 2011 Dec 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

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

Substances

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