The formation of heart DNA adducts in F344 rat following dietary administration of heterocyclic amines.
Most heterocyclic amines formed during the cooking of meat and fish have been shown to form adducts in the livers of rats. Recently, however, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), administered in the diet to Fischer 344 (F344) rats for 4 weeks, was shown to produce the highest levels of adducts in the heart. In the present study 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 2-amino-6-methyldipyrido[1,2-a:1',2'-d]imidazole (Glu-P-1) were given to F344 rats at carcinogenic dose levels (IQ 0.03%, MeIQx 0.04%, Trp-P-1 0.015%, Glu-P-1 0.05%) in the diet for 4 weeks. DNA adducts in the liver and heart were analyzed by 32P-postlabeling. DNA adducts were demonstrated to appear in the hearts of all animals exposed to heterocyclic amines at the following levels: IQ, 1.8 adducts/10(7) nucleotides, MeIQx, 3.8/10(7) ntd, Trp-P-1, 20/10(7) ntd and Glu-P-1, 7.2/10(7) ntd. Values for the heart were 10-20% of the respective liver adduct levels. Heart adducts increased linearly throughout the observed period when MeIQx was administered for up to 40 weeks. When MeIQx feeding was discontinued after 20 weeks and the animals subsequently given the basal diet, the adduct level at 20 weeks did not change during the following 20 weeks. A possible role for heart DNA alterations caused by food-borne heterocyclic amines in the development of age-related myopathies and cardiovascular disease is not inconceivable.
Overvik
E
E
Carcinogenesis Division, National Cancer Center Research Institute, Tokyo, Japan.
Ochiai
M
M
Hirose
M
M
Sugimura
T
T
Nagao
M
M
D000284:Administration, Oral; D000375:Aging; D000588:Amines / Q000494:pharmacology*; D000818:Animals; D002243:Carbolines / Q000494:pharmacology; D004247:DNA / Q000187:drug effects*; D004249:DNA Damage; D004032:Diet; D006321:Heart / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011804:Quinolines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D000588:Amines; D002243:Carbolines; D007093:Imidazoles; D011804:Quinolines; D011810:Quinoxalines; C029216:2-amino-3-methylimidazo(4,5-f)quinoline; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D004247:DNA; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole