Relative activities of methyl methanesulphonate (MMS) as a genotoxin, clastogen and gene mutagen to the liver and bone marrow of Muta™Mouse mice

Tinwell, H.; Lefevre, P.A.; Ashby, John

doi:10.1002/(sici)1098-2280(1998)32:2<163::aid-em12>3.0.co;2-q

Cited by 19 publications

(7 citation statements)

References 25 publications

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“…Only weak mutagenic effects in the liver but no effects in bone marrow were observed in the Muta™mouse [18,124] and negative results in the Big Blue ® mouse [111-113,126]. In the mouse bone marrow micronucleus test this carcinogenic substance induced chromosome aberration [1,127]; other in vitro and in vivo assays clearly supported the clastogenic activity [121,122].…”

Section: Resultsmentioning

confidence: 99%

“…There is evidence that the chromosome mutagenic activity is detectable at much lower doses than the gene mutagenic activity. Tinwell et al (1998) [18] have shown on Muta™mice a weak gene mutagenic effect in the liver but no effect in the bone marrow. The same dose induced in these animals a significant increase in bone marrow micronuclei indicating clear clastogenic activity.…”

Section: Resultsmentioning

confidence: 99%

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et al. 2005

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As part of a larger literature study on transgenic animals in mutagenicity testing, test results from the transgenic mutagenicity assays (lacI model; commercially available as the Big Blue® mouse, and the lacZ model; commercially available as the Muta™Mouse), were compared with the results on the same substances in the more traditional mouse bone marrow micronucleus test. 39 substances were found which had been tested in the micronucleus assay and in the above transgenic mouse systems. Although, the transgenic animal mutation assay is not directly comparable with the micronucleus test, because different genetic endpoints are examined: chromosome aberration versus gene mutation, the results for the majority of substances were in agreement. Both test systems, the transgenic mouse assay and the mouse bone marrow micronucleus test, have advantages and they complement each other. However, the transgenic animal assay has some distinct advantages over the micronucleus test: it is not restricted to one target organ and detects systemic as well as local mutagenic effects.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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et al. 2005

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“…This substance showed mutagenic activity in the Muta™ mouse assay [19] but negative results in the mouse spot test [12,13]. No data on carcinogenicity are available on 4-acetylaminofluorene.…”

Section: Resultsmentioning

confidence: 99%

“…Only weak mutagenic effects were observed in the Muta™ mouse [19,57,75-77] and negative results in the Big Blue ® mouse [63-65,78]. In the mouse spot test this carcinogenic substance is mutagenic [3] as well as in other gene mutation assays in vitro and in vivo [73,74].…”

Section: Resultsmentioning

confidence: 99%

“…However, there is evidence that the chromosome mutagenic activity is detectable at much lower doses than the gene mutagenic activity. Tinwell et al [19] have shown in Muta™ mice a weak gene mutagenic effect in the liver but no effect in the bone marrow. The same dose induced in these animals a significant increase in bone marrow micronuclei indicating clear clastogenic activity.…”

Section: Resultsmentioning

confidence: 99%

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Wahnschaffe¹,

Bitsch²,

Kielhorn³

et al. 2005

J Carcinog

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The mouse spot test, an in vivo mutation assay, has been used to assess a number of chemicals. It is at present the only in vivo mammalian test system capable of detecting somatic gene mutations according to OECD guidelines (OECD guideline 484). It is however rather insensitive, animal consuming and expensive type of test. More recently several assays using transgenic animals have been developed. From data in the literature, the present study compares the results of in vivo testing of over twenty chemicals using the mouse spot test and compares them with results from the two transgenic mouse models with the best data base available, the lacI model (commercially available as the Big Blue® mouse), and the lacZ model (commercially available as the Muta™ Mouse). There was agreement in the results from the majority of substances. No differences were found in the predictability of the transgenic animal assays and the mouse spot test for carcinogenicity. However, from the limited data available, it seems that the transgenic mouse assay has several advantages over the mouse spot test and may be a suitable test system replacing the mouse spot test for detection of gene but not chromosome mutations in vivo.

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