About the Transgenics & In Vivo Mutagenesis SIG

Transgenics & In Vivo Mutagenesis SIG News

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2014 TIVM SIG Agenda for the EMGS Meeting in Orlando!

TIVM SIG Breakfast Meeting Agenda - 2013

The Transgenic and In Vivo Mutagenesis (TIVM) Special Interest Group (SIG) focuses on the development and application of methods to assess mutagenicity in vivo, including laboratory animals and humans.  In the last two decades, transgenic animals, which contain genomic insertions of bacteriophage shuttle vectors, have been used to measure in vivo mutant frequencies. These validated Transgenic Rodent (TGR) animal models are described in OECD Test Guideline 488. These systems allow the identification of mutations in any somatic tissue or male germ cells from which sufficient DNA can be obtained. These TGR models include the Big Blue®mouse and rat, the MutaMouse mouse, the gpt delta mouse and rat, and the lacZ plasmid mouse, among others. More recently, the Pig-a endogenous mutation assay has been developed and is being widely used to assess mutant frequency in the blood of mice, rats, as well as humans. With recent advancements in next generation sequencing (NGS) and epigenetics, powerful new tools are available to investigate alterations in DNA sequence, structure and gene expression in laboratory animals and humans. This promises to revolutionize how we assess genetic damage in order to improve reproductive and cancer risk assessment in humans.


SIG Leaders

Francesco Marchetti, Chair; Mark Fielden, Co-Chair; and Javier Revollo, New Investigator Co-Chair


Files and Images of Interest

EMGS 2013 Annual Meeting SIG Agenda

This file contains the agenda for the Transgenics & In Vivo Mutagenesis SIG meeting in Monterey.

2013-09-17 10:12:09
TIVM SIG Meeting Report

Transgenic and In Vivo Mutagenesis (TIVM) SIG

Breakfast Meeting in Montreal, Canada

Chairs: Manju Manjanatha & Nan Mei, FDA/NCTR, Jefferson, AR

The TIVM SIG convened over breakfast on Sunday October 16, 2011 at 7AM in Montreal. There were about 45 attendees at the event and as the first item of business; new nominations were solicited for the election of new Chairs. However, the attendees, instead of submitting new nominations overwhelmingly voted for the current officers to continue serving the SIG for 2012.

The meeting kicked off with five oral presentations all of which were highly informative and interesting. George Douglas form Health Canada (Retired) announced the successful approval of the TGR assays by the OECD. The first speaker for the morning session was Michelle DeSimone [North Carolina State University, Raleigh, NC, USA, mdesimone123@yahoo.com (Abstract 0065)]. To model inter-individual variation in metabolism, detoxification, transport and genetic heterogeneity of exposed human populations, she developed a knockout mouse and tested with environmentally-relevant doses of carcinogens for toxicity susceptibility. She described how genetic analysis of individual mice within each population in her study would reveal susceptibility loci responsible for the development of human cancer.

Shobhan Gaddameedhi (University of North Carolina, Chapel Hill, NC, USA. shobhan@email.unc.edu, Abstract 0070) presented an exciting study on the role of the circadian clock in UV-induced skin carcinogenesis. Interestingly, UV exposure of mice at 4 AM when repair is at its minimum induced more damage than UV exposure of mice at 4PM when repair is at its peak. At 25 weeks, AM treated mice had two-fold higher carcinomas than PM treated mice suggesting the effect of circadian clock in UV-induced skin carcinogenesis. This study suggests that similar mechanisms may be operating in humans and studying the circadian clock and timing it may be possible to reduce the risk of exposure to sunlight and tanning beds.

Christine Lemieux [Health Canada, Ottawa, ON, Canada, Christine.lemieux@hc-sc.gc.ca(Abstract 0148)] presented a talk on simultaneous measurements of DNA adducts, pig-a and lacZ mutations, and micronuclei induced by 4PAHs. Her study compared the responses obtained with the Pig-a mutation assay to those of the lacZ mutation and the micronucleus assays for PAHs like BaP, DBahA, BaA, etc., in MutaTMMouse models for 28 days. Dose dependent increases in the DNA adducts, and lacZ mutations were seen for the PAHs and also the PAH doubling doses calculated for lacZ mutants were more sensitive than Pig-a DD as Pig-a DD was not significantly different from the lacZ DD for bone marrow for at least two of the PAHs. These studies demonstrated the feasibility of integrating multiple end points into a subchronic study to reduce the number of animals in the study, and that the Pig-a assay may need further validation.

The next speaker was Bryce as Dorothea [D. Torous, Litron Laboratories, Rochester, NY, USA. dtorous@litronlabs.com (Abstract 0164)] was not able to make it to the meeting. Bryce presented another multi-endpoint study on investigation of Chlorambucil genotoxicity using pig-a mutation, micronucleus, and comet assays. The results showed that Chlorambucil is genotoxic in all the end-points used and that the integration of multiple-end points is possible and desirable to conserve animals and reduce the cost of an experiment but results on Comet study should be interpreted in the context of cytotoxicity data especially in a subchronic study when there is no other measurement of cytotoxicity included in the study.

The last but not the least speaker for the morning breakfast session was Chris Hobbs, [ILS, Inc, Research Triangle Park, NC, USA. chobbs@ils-inc.com (Abstract 0199)] who presented a talk entitled "Genotoxicity of styrene-acrylonitrile Trimer in brain, liver, and blood cells of weanling F344 rats”. Styrene-acrylonitrile (SAN) Trimer was identified at a Superfund site in Dover Township, NJ where childhood cancer incidence rates were elevated from 1979-1995. To test the in vivo genotoxicity of this chemical, a combined micronucleus and Comet assays were conducted in weanling male and female F344 rats. The results showed that oral exposure of male and female rats to SAN Timer was genotoxic in multiple tissues as measured by these two assays suggesting that the childhood cancer incidence may have some association with the contamination of this chemical in the Township which needed further investigation.

The meeting was adjourned at 8.30AM.

2011-11-08 09:42:44
Invitation to 2011 TIVM Breakfast Meeting

Transgenic and In vivo Mutagenesis SIG Breakfast meeting in Montreal on October 16, 2011

2011-05-24 13:52:47