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In vivo cytogenetic screening methods for mutagens, with special reference to the micronucleus test

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Abstract

It has been claimed that the micronucleus test (MNT) is a simple and practical in vivo cytogenetic screening method for mutagens. To evaluate the MNT as an initial screening method, mice and Chinese hamsters were treated in vivo with triethylene melamine (0.016, 0.032, 0.062, 0.125, or 0.25 mg/kg), azathioprine (50, 200, or 500 mg/kg), colchicine (0.625, 1.25, or 2.5 mg/kg) or caffeine (100, 200, or 250 mg/kg). The treated animals were examined by means of the MNT, chromosome analysis (CA) and sister chromatid exchange (SCE) scoring. For the MNT and CA, each dose level was applied twice to 3–4 animals with an interval of 24 h. For the SCE test, the animals received a treatment with 5-bromodeoxyuridine (BUDR) and 5-fluorodeoxyuridine (FUDR), during which time the test compounds were administered once.

Triethylene melamine was clearly positive in all three tests, whereas azathioprine was positive in the MNT and CA, but negative in the SCE. Colchicine was positive in the MNT, but negative in the other two tests. Caffeine gave negative results in all three tests. The results indicate that the MNT can detect not only chromosome-breaking agents but also spindle poisons. This is a great advantage over other cytogenetic methods as far as screening is concerned, as is the technical simplicity with which the test can be performed. Furthermore, the basic treatment for the in vivo SCE method using BUDR and FUDR was shown to be positive in the MNT and CA.

A review of the literature dealing with the MNT in which the results of testing 150 agents are reported confirms the present findings, i.e., the usefulness of the MNT for screening clastogens and spindle poisons.

We conclude that, among the various in vivo cytogenetic methods using mammalian somatic cells, the MNT is the most practical when applied as an initial screening test in laboratories in which a large number of compounds are to be tested. Advantages, limitations and function of the MNT are also discussed.

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Tsuchimoto, T., Matter, B.E. In vivo cytogenetic screening methods for mutagens, with special reference to the micronucleus test. Arch Toxicol 42, 239–248 (1979). https://doi.org/10.1007/BF00334837

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  • DOI: https://doi.org/10.1007/BF00334837

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