Detailed review of transgenic rodent mutation assays

Lambert, Iain B.; Singer, Timothy M.; Boucher, Sherri E.; Douglas, George R.

doi:10.1016/j.mrrev.2005.04.002

Cited by 338 publications

(329 citation statements)

References 420 publications

Supporting

Mentioning

316

Contrasting

Unclassified

Order By: Relevance

“…Although the lacZ model does not permit the detection of gene mutations in the ovum per se, Douglas described a method to detect lacZ mutations in granulosa cells, which provide the immediate environment for the ovum in female mice [Yauk et al, 2005]. Lambert et al [2005] have reviewed the use of transgenic rodent assays, including their use in germ-cell studies.…”

Section: Open Discussion Session 2 Research Recommendations For Assesmentioning

confidence: 99%

See 1 more Smart Citation

Assessing human germ‐cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell

Wyrobek

Mulvihill

Wassom

et al. 2007

Environ and Mol Mutagen

View full text Add to dashboard Cite

Birth defects, de novo genetic diseases, and chromosomal abnormality syndromes occur in ~5% of all live births, and affected children suffer from a broad range of lifelong health consequences. Despite the social and medical impact of these defects, and the 8 decades of research in animal systems that have identified numerous germ-cell mutagens, no human germ-cell mutagen has been confirmed to date. There is now a growing consensus that the inability to detect human germ-cell mutagens is due to technological limitations in the detection of random mutations rather than biological differences between animal and human susceptibility. A multidisciplinary workshop responding to this challenge convened at The Jackson Laboratory in Bar Harbor, Maine. The purpose of the workshop was to assess the applicability of an emerging repertoire of genomic technologies to studies of human germ-cell mutagenesis. Workshop participants recommended large-scale human germ-cell mutation studies be conducted using samples from donors with high-dose exposures, such as cancer survivors. Within this high-risk cohort, parents and children could be evaluated for heritable changes in (a) DNA sequence and chromosomal structure, (b) repeat sequences and minisatellites, and (c) global gene expression profiles and pathways. Participants also advocated the establishment of a bio-bank of human tissue samples from donors with well-characterized exposure, including medical and reproductive histories. This mutational resource could support large-scale, multipleendpoint studies. Additional studies could involve the examination of transgenerational effects NIH Public AccessAuthor Manuscript Environ Mol Mutagen. Author manuscript; available in PMC 2007 November 8. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript associated with changes in imprinting and methylation patterns, nucleotide repeats, and mitochondrial DNA mutations. The further development of animal models and the integration of these with human studies are necessary to provide molecular insights into the mechanisms of germcell mutations and to identify prevention strategies. Furthermore, scientific specialty groups should be convened to review and prioritize the evidence for germ-cell mutagenicity from common environmental, occupational, medical, and lifestyle exposures. Workshop attendees agreed on the need for a full-scale assault to address key fundamental questions in human germ-cell environmental mutagenesis. These include, but are not limited to, the following: Do human germ-cell mutagens exist? What are the risks to future generations? Are some parents at higher risk than others for acquiring and transmitting germ-cell mutations? Obtaining answers to these, and other critical questions, will require strong support from relevant funding agencies, in addition to the engagement of scientists outside the fields of genomics and germ-cell mutagenesis.

show abstract

Section: Open Discussion Session 2 Research Recommendations For Assesmentioning

confidence: 99%

“…Transgenic models using reporter genes have the relative advantage of measuring gene mutation directly in sperm; however, such models permit only gene (and not chromosomal) mutations to be measured; the reporter gene is not expressed [Lambert et al, 2005].…”

mentioning

confidence: 99%

Assessing human germ‐cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell

Wyrobek

Mulvihill

Wassom

et al. 2007

Environ and Mol Mutagen

View full text Add to dashboard Cite

show abstract

“…These data show that because independent mutation events can be distinguished, in situ imaging provides a more sensitive method for determining environmentally induced mutations in adult tissues. Interestingly, many previously published mutation studies have been done by analyzing DNA from disaggregated tissue (e.g., Aprt, Tk, Big Blue, Muta Mouse, GptD), [53][54][55] an approach that limits information about the clonal relationship among mutant cells. The observation that in situ analysis is more sensitive than tissue disaggregation for detecting environmentally induced mutations raises the possibility that previous studies of disaggregated tissues may underestimate the impact of some environmental exposures.…”

Section: Advantages Of In Situ Detectionmentioning

confidence: 99%

Applications of Fluorescence for Detecting Rare Sequence Rearrangements In Vivo

Wiktor-Brown

Hendricks²,

Olipitz³

et al. 2006

Cell Cycle

View full text Add to dashboard Cite

“…The lacZ and lacI transgenic rodent systems have proved to be appropriate models for in vivo mutagenesis before tumors develop [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Effects of 1,4-phenylenebis(methylene)selenocyanate on mutagenesis and p53 protein expression in the tongue of lacI rats treated with 4-nitroquinoline-N-oxide

Guttenplan

Chen

Khmelnitsky

et al. 2007

Mutation Research/Genetic Toxicology and Environmental Mutagene

View full text Add to dashboard Cite

Previously we showed that the organoselenium compound, 1,4-phenylenebis(methylene) selenocyanate (p-XSC)1 inhibits 4-nitroquinoline-N-oxide (4-NQO)-induced tongue tumorigenesis in Fisher rats. Here we investigate possible mechanisms of this inhibition by monitoring mutagenesis and p53 protein levels in lacI and conventional Fisher rats treated with: 1) a carcinogenic dose of 4-NQO for 10 weeks in drinking water, 2) 4-NQO + p-XSC (15 ppm as selenium), and 3) 4-NQO followed by p-XSC. For mutagenesis studies, rats were euthanized at 7, 12 or 23 wks after the start of 4-NQO. For studies on p53 levels, rats were euthanized at 11, 15 and 23 wks. Appropriate controls were also monitored. In the 4-NQO-alone groups, the mutant fraction (MF) in the cII gene in tongue increased at least 50 × background level. The MF (in units of mutants/10 5 plaque forming units) for the 7, 12 and 23 week 4-NQO groups were respectively, 184 ± 88, 237 ± 105, 329 ± 110. Thus, mutagenesis increased with length of exposure and post-treatment time. p-XSC modestly (ca. 15 -30%) inhibited mutagenesis under all conditions. The inhibition reached significance at the last time point. When p-XSC was administered after 4-NQO, the MF was also modestly reduced. In 4-NQOalone animals, levels of p53 in tongue (determined by Western blotting) were 1, 1.5 and 2.4 control levels at 10, 15 and 23 weeks respectively. In the p-XSC + 4-NQO group, the enhancement in p53 levels by 4-NQO treatment was decreased about 90% at 15 weeks and 45% (P < 0.05) at 23 weeks, and by slightly smaller percentages in corresponding post-treatment groups. p-XSC alone did not alter p53 levels. As p53 levels generally increase in response to DNA damage, these results suggest that p-XSC reduces 4-NQO-induced DNA damage, resulting in reduced 4-NQO-induced mutagenesis and carcinogenesis. However, the fact that p-XSC is also effective when administered after 4-NQO, suggests additional mechanisms of inhibition exist.

show abstract

Detailed review of transgenic rodent mutation assays

Cited by 338 publications

References 420 publications

Assessing human germ‐cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell

Assessing human germ‐cell mutagenesis in the Postgenome Era: A celebration of the legacy of William Lawson (Bill) Russell

Applications of Fluorescence for Detecting Rare Sequence Rearrangements In Vivo

Effects of 1,4-phenylenebis(methylene)selenocyanate on mutagenesis and p53 protein expression in the tongue of lacI rats treated with 4-nitroquinoline-N-oxide

Contact Info

Product

Resources

About