DNA adduct formation of hepatocarcinogenic aromatic amines in rat liver: effect of cytochrome P450 inducers.
F344 rats were treated with an i.p. injection of 2-amino-6- methyldipyrido[1,2-a:3',2'-d]imidazole (Glu P-1) or 3-methoxy-4-aminoazobenzene (3-MeO-AAB) and examined for the formation of the DNA adduct in the liver. To examine the effect of pretreatment with a cytochrome P450 (CYP) inducer on the formation of DNA adduct, these rats were pretreated with 3-methylcholanthrene (MC; CYP1A1/1A2 inducer) or phenobarbital (PB; CYP2B inducer). Administration of Glu P-1 and 3-MeO-AAB gave 2 and 5 adducts, respectively, as determined by 32P-postlabeling assay. By Glu P-1 administration, pretreatment of rats with MC, but not with PB, increased the total amount of DNA adducts including 3 new adducts as minor products. In contrast, pretreatment of rats with PB increased the total amount of DNA adducts derived by 3-MeO-AAB. The increase of aromatic amine DNA adducts by pretreatment with a CYP inducer was proportional to the activity of induced CYP isozyme(s) responsible for the mutagenic activation of each aromatic amine.
Degawa
M
M
Department of Hygienic Chemistry, Tohoku University, Sendai, Japan.
Kojima
M
M
Yoshinari
K
K
Tada
M
M
Hashimoto
Y
Y
D000818:Animals; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004247:DNA / Q000378:metabolism*; D004790:Enzyme Induction; D007093:Imidazoles / Q000378:metabolism / Q000633:toxicity; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008297:Male; D008748:Methylcholanthrene / Q000378:metabolism / Q000633:toxicity; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D010634:Phenobarbital / Q000378:metabolism / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity
D002273:Carcinogens; D007093:Imidazoles; D008748:Methylcholanthrene; D010128:p-Aminoazobenzene; C023785:2-amino-6-methyldipyrido(1,2-a-3',2'-d)imidazole; C044436:3-methoxy-4-aminoazobenzene; D004247:DNA; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital