Mutant frequency of lacI in transgenic mice following benzo[a]pyrene treatment and partial hepatectomy

Shane, Barbara S.; Lockhart, Ann-Marie; Winston, Gary W.; Tindall, Kenneth R.

doi:10.1016/s0027-5107(97)00004-3

Cited by 32 publications

(12 citation statements)

References 30 publications

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“…This hypothesis is also supported by another study, in which MMS could induce liver micronuclei only in conjunction with partial hepatectomy [Tates and den Engelse, 1989]. Recently, Shane [1997] reported that a partial hepatectomy together with B[a]P treatment result in a modest increase in the mutation frequency (2.2-fold), although that was not statistically different from that of B[a]P treatment without a partial hepatectomy. In bacterial and even experiments in tissue culture, the clonality in analyzing mutations is readily avoided by using numerous small cultures and taking only a single mutant from each.…”

Section: The Question Of Clonalitysupporting

confidence: 56%

Spontaneous mutation of the lacI transgene in rodents: Absence of species, strain, and insertion‐site influence

Zhang

Glickman

Boer

2001

Environ and Mol Mutagen

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Comparison of spontaneous mutation spectra derived from different transgenic constructs can provide valuable insights for interpreting the mechanisms of spontaneous mutation. In this study, spontaneous mutation frequencies and spectra of the lacI transgene are compared in the liver of C57BL/6, B6C3F1, and BC-1 mice and F344 rats. Before correction for clonal expansion, the mutant frequency varied from 2.6 +/- 0.45 to 5.0 +/- 2.4 x 10(-5). Correction for potential clonal expansion reduced the range in mutation frequency to between 2.3 +/- 0.45 and 3.5 +/- 2.0 x 10(-5). There is thus no statistical difference in spontaneous mutation frequency between the different strains and species. G:C --> A:T transitions and to a lesser extent, G:C --> T:A transversions dominate the mutational spectra in all of these animals. In three strains of mice, G:C --> A:T transitions account for 50.7-53.3% of mutation, 81.7-83.8% of which involve CpG sites, whereas G:C --> T:A transversions account for 17.8-32.9% of mutations with 43.2-50.0% found at CpG sites. In rats, G:C --> A:T transitions account for 38.0% of the spectra, 70.0% of which involve CpG sites, whereas G:C --> T:A transversions account for 23.0% of the spectra, 70.0% of which involve CpG sites. The distribution of other classes of mutations is also very similar. We conclude that, despite reports about species and strain differences in induced mutation, spontaneous mutations in the lacI transgene appear to be similar, regardless of genomic location, rodent strain, or species. In addition to insights into spontaneous mutation, this study also provides essential data for comparison with and interpretation of induced mutations.

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Section: The Question Of Clonalitysupporting

confidence: 56%

Spontaneous mutation of the lacI transgene in rodents: Absence of species, strain, and insertion‐site influence

Zhang

Glickman

Boer

2001

Environ and Mol Mutagen

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“…The mutagenicity of B[a]P has previously been determined in the liver, spleen, forestomach, and bone marrow using oral administration or i.p. injection in the Big Blue mouse [Skopek et al, 1996;Shane et al, 1997Shane et al, , 2000, Muta Mouse [Mientjes et al, 1996;Rompelberg et al, 1996;Hakura et al, 1998;Kosinska et al, 1999], and the rpsL transgenic mouse [Muto et al, 1999]. In these reports, the authors did not determine whether the mutant frequency depended on the dose of B[a]P except for one study using spleen T-cells [Skopek et al, 1996].…”

Section: Discussionmentioning

confidence: 99%

In vivo mutagenesis induced by benzo[a]pyrene instilled into the lung ofgpt delta transgenic mice

Hashimoto

Amanuma

Hiyoshi

et al. 2005

Environ. Mol. Mutagen.

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Benzo[a]pyrene (B[a]P) is a ubiquitous airborne pollutant whose mutagenicity has been evaluated previously by oral and intraperitoneal administration to experimental animals. In this study, mutagenesis in the lungs, the target organ of air pollutants, was examined after a single intratracheal instillation of 0-2 mg B[a]P into gpt delta transgenic mice. Intratracheal injection of B[a]P resulted in a statistically significant and dose-dependent increase in gpt mutant frequency as measured by 6-thioguanine selection. The mutant frequencies at B[a]P doses of 0.5, 1, and 2 mg were 2.8, 4.2, and 6.8 times higher than the frequency seen in nontreated mice (0.60 +/- 0.13 x 10(-5)). The most frequent mutations induced by B[a]P treatment were G:C-->T:A transversions, which are characteristic of B[a]P mutagenesis in other models, and single-base deletions of G:C base pairs. To characterize the hotspots of B[a]P-induced mutations in the gpt gene, we analyzed sequences adjacent to the mutated G:C base pairs. Guanine bases centered in the nucleotide sequences CGT, CGA, and CGG were the most frequent targets of B[a]P. Our results indicate that intratracheal instillation of B[a]P into gpt delta mice causes a dose-dependent increase in gpt mutant frequency in the lung, and that the predominant mutation induced is G:C-->T:A transversion.

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“…Genomic DNA was isolated from the spleen of offspring identified as lacI carriers, according to a previously described protocol [Shane et al, 1997]. Subsequently, DNA was also isolated from the kidney, liver, and ovary or testis of those mice with a high mutant frequency in the spleen.…”

Section: Purification Of Genomic Dna For Laci Mutation Analysismentioning

confidence: 99%

Transmission of mutations in the lacI transgene to the offspring of ENU‐treated Big Blue® male mice

Barnett

Tyl

Shane

et al. 2002

Environ and Mol Mutagen

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The purpose of the study was to determine: 1) if male germ cells of Big Blue mice carrying newly induced mutations in the lacI transgene were effective in fertilization; 2) if offspring arising from such mutant sperm had the mutation in germ cells and multiple somatic tissues; and 3) how the frequency of mutants induced in the lacI transgene compared to the frequency induced in endogenous genes traditionally employed to study germ cell mutagenesis in mice. Male B6C3F(1) mice hemizygous for the lambda/lacI transgene were treated weekly with 100 mg/kg body weight of the mammalian germ cell mutagen N-ethyl-N-nitrosourea (ENU). The cumulative dose for each treated animal was 300 mg ENU/kg body weight. Ten weeks later the treated mice were mated to T stock females and the resulting offspring were screened for specific-locus mutations at six loci affecting external appearance, as well as for mutations in the lacI transgene in multiple somatic tissues and germ cells. Five offspring carrying recessive specific-locus mutations were observed among 597 offspring screened (mutant frequency = 139.6 x 10(-5) per locus). Four offspring carrying lacI mutations were observed among 280 offspring screened (mutant frequency = 35.7 x 10(-5) per locus (assuming 40 target loci)). Each of the four lacI mutant offspring carried a different mutation. Three of the mutations were A:T-->G:C transitions and one a G:C-->A:T transition. Consistent with the expectation that a mutation induced in a parental germ cell and transmitted to a conceptus would exist in every cell of the offspring, each mutant mouse had identical mutations in all somatic tissues sampled, as well as in its germ cells. These data provide preliminary evidence for the biological validity of assessing induced, heritable mutations using transgenic mice, without the need for generating an F(1) generation.

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Mutant frequency of lacI in transgenic mice following benzo[a]pyrene treatment and partial hepatectomy

Cited by 32 publications

References 30 publications

Spontaneous mutation of the lacI transgene in rodents: Absence of species, strain, and insertion‐site influence

Spontaneous mutation of the lacI transgene in rodents: Absence of species, strain, and insertion‐site influence

In vivo mutagenesis induced by benzo[a]pyrene instilled into the lung ofgpt delta transgenic mice

Transmission of mutations in the lacI transgene to the offspring of ENU‐treated Big Blue® male mice

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