Mutagenicity of 4-nitroquinoline 1-oxide in the MutaMouse.
As part of a collaborative study, the Mammalian Mutagenesis Study Group (MMS), a sub-organization of the Environmental Mutagen Society of Japan (JEMS) conducted mutagenicity tests in MutaMouse. Using a positive selection method, we studied the organ-specificity and time dependence of mutation induction by 4-nitroquinoline 1-oxide (4NQO). A single dose of 4NQO was administered intraperitoneally (7.5 or 15 mg/kg) or orally (200 mg/kg) to groups of male mice. On days 7, 14 and 28 after treatment, we isolated the liver, kidney, lung, spleen, bone marrow, testis and stomach in the intraperitoneal administration experiment and the liver, lung, bone marrow, testis and stomach in the oral administration experiment. In addition, we performed the peripheral blood micronucleus test to evaluate clastogenicity. In the mice treated intraperitoneally at 7.5 mg/kg, we found increased mutant frequency (MF) only in the lung, where the MF did not vary with expression time. In the mice treated at 15 mg/kg, we found increased MF in the liver, bone marrow and lung. In orally treated mice, the MF was high in the lung and liver and very high in the bone marrow and stomach while the increase in the testis was negligible. As the expression time was prolonged, the MF tended to increase in the liver, decrease in the bone marrow, and remain stable in the lung, testis and stomach. The incidence of micronucleus induction in peripheral blood cells was significantly increased (p<0.01) in the 4NQO groups when compared with the vehicle control group by intraperitoneal treatment. Thus, these assay systems appeared to be of use in detecting not only genetic mutation but also chromosomal aberration.
Nakajima
M
M
Biosafety Research Center, Foods, Drugs and Pesticides, 582-2, Shioshinden, Fukude-cho, Iwata-gun, Shizuoka, Japan. nakajima@anpyo.or.jp
Kikuchi
M
M
Saeki
K
K
Miyata
Y
Y
Terada
M
M
Kishida
F
F
Yamamoto
R
R
Furihata
C
C
Dean
S W
SW
D015112:4-Nitroquinoline-1-oxide / Q000633:toxicity*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D007763:Lac Operon; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation; D009928:Organ Specificity; D013997:Time Factors
D002273:Carcinogens; D009153:Mutagens; D015112:4-Nitroquinoline-1-oxide