N-Nitrosodi-n-propylamine induces organ specific mutagenesis with specific expression times in lacZ transgenic mice.
The mutagenic and clastogenic effects of N-nitrosodi-n-propylamine (NDPA) in lacZ transgenic mice (MutaMouse) were investigated as a part of the second collaborative study of the transgenic mouse mutation assay by a subgroup of the Mammalian Mutagenesis Study Group, a suborganization of the Environmental Mutagen Society of Japan. Male MutaMouse mice were administered NDPA intraperitoneally at a dose of 250 mg/kg, which is half of the LD(50) of the compound. The clastogenicity of NDPA was examined by the peripheral blood micronucleus test just before and at 24, 48 and 72 h after the treatment. The mutant frequencies in the bone marrow, liver, lung, kidney and urinary bladder were examined by the positive selection method for lacZ kidney. These findings demonstrate that NDPA induces organ-specific mutagenesis with specific expression times, and that the mutagenicity of NDPA in lacZ transgenic mice is consistent with its carcinogenicity.
Itoh
S
S
Drug Safety Research Laboratory, Daiichi Pharmaceutical, 16-13 Kita-Kasai 1-Chome, Edogawa-ku, Tokyo, Japan. itohsudk@daiichipharm.co.jp
Miura
M
M
Itoh
T
T
Miyauchi
Y
Y
Suga
M
M
Takahashi
Y
Y
Kasahara
Y
Y
Yamamura
E
E
Hirono
H
H
Shimada
H
H
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D007763:Lac Operon; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D015162:Micronucleus Tests; D016296:Mutagenesis; D009153:Mutagens / Q000633:toxicity*; D009602:Nitrosamines / Q000633:toxicity*; D009928:Organ Specificity
D002273:Carcinogens; D009153:Mutagens; D009602:Nitrosamines; C013161:N-nitroso(di-n-propyl)amine