Mutagenicity of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) in the new gpt delta transgenic mouse.
Gender differences and organ specificity of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mutagenesis were examined with the new gptdelta transgenic mouse (T. Nohmi, M. Katoh, H. Suzuki, M. Matsui, M. Yamada, M. Watanabe, M. Suzuki, N. Horiya, O. Ueda, T. Shibuya, H. Ikeda, T. Sofuni, A new transgenic mouse mutagenesis test system using Spi-and 6-thioguanine selections (Environ. Mol. Mutagen. 28 (1996) 465-470). In this mouse model, two distinct selections are employed to efficiently detect different types of mutations, i.e 6-thioguanine (6-TG) selection for point mutations and Spi-selection for deletions, respectively. In both selections, the highest mutant frequencies were observed in colon, followed by in spleen and liver. No increases in mutations were observed in testis, brain and bone marrow in PhIP-treated male mice. No significant differences in 6-TG and Spi- mutant frequencies were observed in colon and liver between male and female treated mice. The correlation between PhIP-induced mutagenesis and carcinogenesis in colon is discussed.
Masumura
K
K
Division of Genetics and Mutagenesis, National Institute of Health Sciences, Tokyo, Japan.
Matsui
K
K
Yamada
M
M
Horiguchi
M
M
Ishida
K
K
Watanabe
M
M
Ueda
O
O
Suzuki
H
H
Kanke
Y
Y
Tindall
K R
KR
Wakabayashi
K
K
Sofuni
T
T
Nohmi
T
T
D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D003106:Colon / Q000187:drug effects / Q000502:physiology; D029968:Escherichia coli Proteins; D005260:Female; D007093:Imidazoles / Q000633:toxicity*; D008099:Liver / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D010430:Pentosyltransferases; D011506:Proteins; D013154:Spleen / Q000187:drug effects / Q000502:physiology
D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D007093:Imidazoles; D009153:Mutagens; D011506:Proteins; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D010430:Pentosyltransferases; C071962:Gpt protein, E coli