32P-postlabeling analysis of DNA adducts in rat stomach with 1-nitrosoindole-3-acetonitrile, a direct-acting mutagenic indole compound formed by nitrosation.
Modification of DNA by a direct-acting mutagen, 1-nitrosoindole-3-acetonitrile, which is formed from indole-3-acetonitrile upon nitrite treatment, was investigated. 32P-Postlabeling analysis clearly demonstrated the formation of DNA adducts in the stomach of rats after intragastric administration of 1-nitrosoindole-3-acetonitrile. The level of DNA adducts in both the forestomach and glandular stomach 2 h after administration of 100 mg/kg body weight of the compound was about one adduct per 10(7) nucleotides. The DNAs of the forestomach and glandular stomach gave six common spots on two-dimensional chromatography, three of which were also produced by in vitro reaction of this compound with DNA. Thus, 1-nitrosoindole-3-acetonitrile can form DNA adducts in vivo and in vitro. No DNA adducts were detected after treatment with the non-nitrosated compound indole-3-acetonitrile both in vivo and in vitro. These results suggest that 1-nitrosoindole-3-acetonitrile has the in vivo tumor initiating activity in the stomach.
Yamashita
K
K
Biochemistry Division, National Cancer Center Research Institute, Tokyo, Japan.
Wakabayashi
K
K
Kitagawa
Y
Y
Nagao
M
M
Sugimura
T
T
D000097:Acetonitriles / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009153:Mutagens / Q000378:metabolism*; D010761:Phosphorus Radioisotopes; D051381:Rats; D011916:Rats, Inbred F344; D012016:Reference Values
D000097:Acetonitriles; D002273:Carcinogens; D009153:Mutagens; D010761:Phosphorus Radioisotopes; D004247:DNA; C053072:1-nitrosoindole-3-acetonitrile