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Mutagenicity of 4-nitroquinoline 1-oxide in the MutaMouse

M Nakajima1, M Kikuchi, K Saeki

  • 1Biosafety Research Center, Foods, Drugs and Pesticides, 582-2, Shioshinden, Fukude-cho, Iwata-gun, Shizuoka, Japan. nakajima@anpyo.or.jp

Mutation Research
|October 16, 1999
PubMed

Insights

The Mammalian Mutagenesis Study Group investigated 4-nitroquinoline 1-oxide (4NQO) mutagenicity in MutaMouse, revealing organ-specific mutations and chromosomal aberrations. 4NQO induced mutations in the lung, liver, bone marrow, and stomach, with varying time-dependent effects.

Area of Science:

  • Toxicology
  • Genetics
  • Pharmacology

Background:

  • The Mammalian Mutagenesis Study Group (MMS) of the Environmental Mutagen Society of Japan (JEMS) conducted mutagenicity tests.
  • Understanding chemical-induced mutations and their organ-specificity is crucial for risk assessment.

Purpose of the Study:

  • To investigate the organ-specificity and time dependence of mutation induction by 4-nitroquinoline 1-oxide (4NQO) in MutaMouse.
  • To evaluate the utility of assay systems for detecting genetic mutations and chromosomal aberrations.

Main Methods:

  • MutaMouse model with a positive selection method.
  • Administration of 4NQO via intraperitoneal or oral routes at different doses.
  • Isolation of multiple organs (liver, kidney, lung, spleen, bone marrow, testis, stomach) at various time points (7, 14, 28 days).
  • Peripheral blood micronucleus test for clastogenicity assessment.

Main Results:

  • Increased mutant frequency (MF) observed in the lung after intraperitoneal 4NQO administration (7.5 mg/kg).
  • MF increased in the liver, bone marrow, and lung after higher intraperitoneal doses (15 mg/kg).
  • Oral 4NQO administration resulted in high MF in the bone marrow and stomach, moderate in the lung and liver, and negligible in the testis.
  • Prolonged expression time showed increasing MF in the liver, decreasing in bone marrow, and stable in lung, testis, and stomach.
  • Significant increase in micronucleus induction in peripheral blood cells indicated clastogenicity.

Conclusions:

  • 4NQO exhibits distinct organ-specific mutagenicity and time-dependent effects in MutaMouse.
  • The assay systems are effective in detecting both gene mutations and chromosomal aberrations induced by chemical agents.
  • Findings contribute to understanding the genotoxic potential of 4NQO and validating mutagenicity testing strategies.

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