Temporal and molecular characteristics of lacZ mutations in somatic tissues of transgenic mice

Environmental and Molecular Mutagenesis
G R DouglasJ A Gossen

Abstract

In order to help establish criteria for optimizing protocols for in vivo mutation studies, lacZ transgenic mice (Muta mouse) were treated with five consecutive daily doses of ethylnitrosourea (50 mg/kg), sampled at times up to 55 days after treatment, and mutant frequencies and DNA sequences determined for liver and bone marrow. In the bone marrow, the mutant frequency rose very rapidly in the first 5 days after treatment to 34 times the control frequency. Subsequently, there was a brood peak where the mutant frequency did not vary significantly, although it did appear to begin to decline after 45 days. In contrast, in the liver, the peak mutant frequency (11 times the control frequency) was not achieved until 35 days, after which there appeared to be a slow decline up to 55 days, which was not statistically significant. Once the maximum mutant frequency was reached, the mutation spectra in the two tissues were indistinguishable. In contrast to the G:C-->A:T transitions in 5'-CpG sites characteristic of untreated mice, A:T-->T:A transversions and A:T-->G:C transitions were prominent in both liver and bone marrow of ENU-treated mice, suggesting the involvement of unrepaired O2- and O4-ethylthymine adducts. In addition, G:C-->T:A...Continue Reading

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Citations

Jan 1, 1996·Environmental and Molecular Mutagenesis·N J Gorelick, J C Mirsalis
Feb 17, 1998·Environmental and Molecular Mutagenesis·E J MientjesJ H van Delft
Aug 27, 1999·Environmental and Molecular Mutagenesis·K MasumuraT Nohmi
Mar 29, 2000·Environmental and Molecular Mutagenesis·J A HeddleN Yajima
Jan 29, 2003·Environmental and Molecular Mutagenesis·John A HeddleGeorge R Douglas
Apr 30, 2003·Environmental and Molecular Mutagenesis·Hiroyuki HayashiTakehiko Nohmi
Jun 26, 2001·Environmental and Molecular Mutagenesis·R R SwigerJ A Heddle
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Sep 19, 2017·Environmental and Molecular Mutagenesis·Takafumi NakayamaShizuko Kakinuma
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Jun 13, 2020·Chemical Research in Toxicology·Vernon E WalkerGeorge R Douglas

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