Formation and removal of DNA adducts in target and nontarget tissues of rats administered multiple doses of 2-acetylaminophenanthrene.
2-Acetylaminophenanthrene (2-AAP) is carcinogenic for the mammary gland, small intestine and ear duct in rats, but is not hepatocarcinogenic. In order to understand the tissue specificity of tumor induction, the formation and removal of DNA adducts in target and nontarget tissues have been compared in rats administered 2-AAP. Male and female Sprague--Dawley rats were treated i.p. with up to four weekly doses of 5 mg 2-AAP per kg body weight. 32P-Post-labeling analysis of the DNA from all tissues showed two predominant adducts (greater than 85-95% of the total binding) and at least four minor adducts. By comparing the results obtained from reacting N-hydroxy-2-aminophenanthrene with DNA at pH 5, the major adducts were identified as N-(deoxyadenosine-8-yl)-2-aminophenanthrene and 1-(deoxyguanosin-N2-yl)-2-aminophenanthrene. Two minor adducts, N-(deoxyadenosine-8-yl)-2-aminophenanthrene and 1-(deoxyadenosin-N6-yl)-2-aminophenanthrene, were also formed in the in vitro reactions. The distribution of adducts, extent of binding and adduct persistence were similar between target and nontarget tissues, which indicates that the tissue specificity of 2-AAP for tumor induction is due to factors in addition to adduct formation.
Gupta
R C
RC
Department of Preventive Medicine, University of Kentucky, Lexington 40536.
Earley
K
K
Fullerton
N F
NF
Beland
F A
FA
D000818:Animals; D002273:Carcinogens; D002851:Chromatography, High Pressure Liquid; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D007421:Intestine, Small / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008321:Mammary Glands, Animal / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects; D010616:Phenanthrenes / Q000008:administration & dosage*; D051381:Rats; D013154:Spleen / Q000187:drug effects; D014018:Tissue Distribution; D001743:Urinary Bladder / Q000187:drug effects
D002273:Carcinogens; D010616:Phenanthrenes; C026364:2-acetamidophenanthrene