M. Degawa et al., DNA ADDUCT FORMATION OF HEPATOCARCINOGENIC AROMATIC-AMINES IN RAT-LIVER - EFFECT OF CYTOCHROME-P450 INDUCERS, Cancer letters, 79(1), 1994, pp. 77-81
F344 rats were treated with an i.p. injection of amino-6-methyldipyrid
o[1,2-alpha: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 l
iver. To examine the effect of pretreatment with a cytochrome p450 (CY
P) inducer on the formation of DNA adduct, these rats were pretreated
with 3-methylcholanthrene (MC; CYP1A1/1A2 inducer) or phenobarbital (P
B; CYP2B inducer). Administration of Glu P-1 and 3-MeO-AAB gave 2 and
5 adducts, respectively as determined by P-32-postlabeling assay. By G
lu P-1 administration, pretreatment of rats with MC, but not with PB,
increased the total amount of DNA adducts including 3 new adducts as m
inor products. In contrast, pretreatment of rats with PB increased the
total amount of DNA adducts derived by 3-MeO-AAB. The increase of aro
matic amine DNA adducts by pretreatment with a CYP inducer was proport
ional to the activity of induced CYP isosyme(s) responsible for the mu
tagenic activation of each aromatic amine.