Heterocyclic amine-DNA adducts analyzed by 32P-postlabeling method.
DNA adducts formed by 12 heterocyclic amines were analyzed by 32P-postlabeling method. Several DNA adducts were detected in rat liver by administration of each heterocyclic amine. Total adduct levels ranged from 0.5 for 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) to more than 250 for 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) per 10(7) nucleotides 24 hr after intragastric administration of these compounds. The N-hydroxy derivative of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) was reactive toward DNA in vitro to form adducts. Addition of acetic anhydride to N-OH-MeIQx greatly enhanced its reactivity to DNA. 32P-Postlabeling analysis revealed that the MeIQx-DNA adducts formed in vivo and in vitro were identical. Thus, MeIQx would be metabolized in vivo to N-hydroxy form and further esterified to produce more reactive species, such as N-acetoxy form, which modify DNA to form adducts.
Yamashita
K
K
Biochemistry Division, National Cancer Center Research Institute, Tokyo, Japan.
Umemoto
A
A
Grivas
S
S
Kato
S
S
Sato
S
S
Sugimura
T
T
D000588:Amines / Q000378:metabolism*; D000818:Animals; D004247:DNA / Q000378:metabolism*; D006571:Heterocyclic Compounds / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D010761:Phosphorus Radioisotopes; D011865:Radioisotope Dilution Technique; D051381:Rats; D011916:Rats, Inbred F344
D000588:Amines; D006571:Heterocyclic Compounds; D010761:Phosphorus Radioisotopes; D004247:DNA