Evidence for in vivo non-mutagenicity of the carcinogen hydrazine sulfate in target tissues of lacZ transgenic mice

Transgenic mouse models permit the confirmation of in vitro mutagenicity in vivo without the constraints in the selection of tissues imposed by other in vivo assays. This feature is of particular importance in the determination of mutagenicity in the target tissues of carcinogens, especially those t...

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Bibliographic Details
Published in:Carcinogenesis (New York) 1995-04, Vol.16 (4), p.801-804
Main Authors: Douglas, George R., Gingerich, John D., Soper, Lynda M.
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Biological and medical sciences
Bone Marrow - drug effects
Carcinogens - toxicity
Chemical mutagenesis
Hydrazines - toxicity
In Vitro Techniques
Lac Operon - drug effects
Liver - drug effects
Lung - drug effects
Medical sciences
Mice
Mice, Transgenic
Mutagens - toxicity
Toxicology
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Summary:Transgenic mouse models permit the confirmation of in vitro mutagenicity in vivo without the constraints in the selection of tissues imposed by other in vivo assays. This feature is of particular importance in the determination of mutagenicity in the target tissues of carcinogens, especially those that are in vitro mutagens. Such information is critical in the determination of whether a chemical is carcinogenic via a genotoxic or non-genotoxic mechanism. Hydrazine sulfate is an in vitro mutagen that induces lung and liver tumours in mice. Transgenic mice from strain 40.6 (MutaTMmouse) were administered single oral doses up to a toxic concentration (400 mg/kg). No dose induced any lacZ mutations in lung, liver or bone marrow. Since the highest single dose used is higher than the cumulative dose that induced tumours in previous studies, it may be that either hydrazine sulfate is genotoxic in target tissues in vivo only when given in multiple doses or that it is a nongenotoxic carcinogen.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/16.4.801