Genotoxicity and cell proliferative activity of a nitrosated Oroxylum indicum Vent fraction in the pyloric mucosa of rat stomach.
In vivo genotoxic activity and cell proliferative activity were examined in the stomach mucosa of male F344 rats by in vivo short-term methods after oral administration of a nitrosated Oroxylum indicum Vent (OiV) fraction, which had been found to be mutagenic without S9 mix to Salmonella typhimurium TA98 and TA100. Administration of the nitrosated OiV fraction at doses of 1 and 2 g/kg body weight induced dose-dependent DNA single-strand scission (p less than 0.02), determined by the alkaline elution method, in the stomach pyloric mucosa 2 h after its administration: a dose of 2 g/kg body weight induced an 18-fold increase in the DNA elution rate constant. Administration of the nitrosated OiV fraction at doses of 0.7-2.8 g/kg body weight also induced dose-dependent increases, up to 11-fold (p less than 0.05), in replicative DNA synthesis in the stomach pyloric mucosa 16 h after its administration. Moreover administration of the nitrosated OiV fraction at doses of 0.25-2.0 g/kg body weight induced dose-dependent increases, up to 100-fold, in ornithine decarboxylase activity in the stomach pyloric mucosa with a maximum 4 h after its administration. These results demonstrate that the nitrosated OiV fraction has genotoxic and cell proliferative activity in the pyloric mucosa of rat stomach in vivo.
Biochemistry and Chemical Carcinogenesis Section, Research Division, National Cancer Institute, Bangkok, Thailand.
A
A
Tepsuwan
C
C
Furihata
W
W
Rojanapo
T
T
Matsushima
D000284:Administration, Oral; D000818:Animals; D002455:Cell Division / Q000187:drug effects*; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects; D004277:DNA, Single-Stranded / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D009152:Mutagenicity Tests; D015538:Nitrosation; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D010936:Plant Extracts / Q000009:adverse effects; D010946:Plants, Medicinal; D051381:Rats; D011916:Rats, Inbred F344
D004277:DNA, Single-Stranded; D010936:Plant Extracts; D009955:Ornithine Decarboxylase