Transgenic models for detection of mutations in tumors and normal tissues of rodents

Toxicology Letters
J C Mirsalis

Abstract

Transgenic rodents that contain easily retrievable target genes allow the rapid quantitation of mutations in any tissue from which DNA can be isolated. We are using the Stratagene Big Blue transgenic mouse system that contains a lacI target and an alpha lacZ reporter gene to study the parameters that affect mutations. We have evaluated a number of chemicals to determine mutant frequency (MF) in specific target tissues of C57Bl/6 and B6C3F1 mice. The correlation between mutagenesis and carcinogenesis in this system is excellent. For example, the liver carcinogen dimethylnitrosamine produces significant increases in MF in mouse liver, whereas the nonhepatocarcinogenic mutagen methylmethane sulfonate does not. We have also evaluated the induction of mutations by radiation and demonstrated that this system is suitable for the study of agents that produce deletion mutations. This system is also useful for studying changes in MF in developing tumors. We have used an initiation-promotion protocol to induce hepatocellular carcinomas, and we then measured MF in normal liver, tumors, and metastases from these mice. Animals initiated with diethylnitrosamine maintain an elevated MF in normal liver, even 1 year after initiation. This MF inc...Continue Reading

References

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Citations

Feb 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Shiquan LiuGlenn Merlino
Mar 4, 2009·Proceedings of the National Academy of Sciences of the United States of America·Patricia MurpheyJohn R McCarrey
Nov 14, 1997·Regulatory Toxicology and Pharmacology : RTP·T J FlammangP P Fu
Sep 29, 2005·Radiation Research·Polly Y ChangRupa Doppalaudi
Jun 7, 2005·Advances in Space Research : the Official Journal of the Committee on Space Research (COSPAR)·E BehraveshS Gonda
Mar 29, 2000·Environmental and Molecular Mutagenesis·J A HeddleN Yajima
Apr 26, 2005·International Journal of Cancer. Journal International Du Cancer·Erzsébet Papp-SzabóBrenda L Coomber
Jan 29, 2003·Environmental and Molecular Mutagenesis·John A HeddleGeorge R Douglas

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