期刊
CANCER LETTERS
卷 318, 期 2, 页码 206-213出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2011.12.022
关键词
Aromatic amine; Chemical carcinogen; Arylamine N-acetyltransferase; DNA adduct; Liver cancer; Sex differences
类别
资金
- Canadian Institutes of Health Research
- National Cancer Institute of Canada
- USPHS from the National Cancer Institute [R01-CA034627]
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. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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