TY - JOUR
T1 - DNA adduct formation of hepatocarcinogenic aromatic amines in rat liver
T2 - effect of cytochrome P450 inducers
AU - Degawa, Masakuni
AU - Kojima, Misaki
AU - Yoshinari, Kouichi
AU - Tada, Mariko
AU - Hashimoto, Yoshiyuki
N1 - Funding Information:
This work wass upportedin part by a Grant-in-Aid for Cancer Researchf rom the Ministry of Education,S ciencea nd Culture, Japan.
PY - 1994/4/29
Y1 - 1994/4/29
N2 - 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 isosyme(s) responsible for the mutagenic activation of each aromatic amine.
AB - 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 isosyme(s) responsible for the mutagenic activation of each aromatic amine.
KW - 2-amino-6-methyldipyrido[1,2-a:3′,2′-d]imidazole
KW - 3-methoxy-4-amino-azobenzene
KW - Cytochrome P450
KW - DNA adduct
KW - P-Postlabeling
KW - Rat liver
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U2 - 10.1016/0304-3835(94)90066-3
DO - 10.1016/0304-3835(94)90066-3
M3 - Article
C2 - 8187057
AN - SCOPUS:0028268710
VL - 79
SP - 77
EP - 81
JO - Cancer Letters
JF - Cancer Letters
SN - 0304-3835
IS - 1
ER -
