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Newsletter, April 26, 2000

Environmental Mutagen Society Special Interest Group in:
Transgenic and In Vivo Mutagenesis

This is a report on the meeting of the Transgenics Special Interest Group held April 13, at the EMS meeting in New Orleans.

Standard Disclaimer :  This Newsletter does not necessarily reflect the opinions or positions of the EMS or its members. Any errors or omissions are strictly on the part of the secretary.

Business Stuff :

(not arranged exactly in order of ocurrence)

Meeting was brought to order by John Heddle [jheddle@yorku.ca], acting as chair.

Attendance was recorded by a hand-out email list : 29 people recorded their email address.

JH proposed broadening the appeal of of the group, in part by modifying or changing it's name. After some discussion, the name was changed to Transgenic and In Vivo Mutagenesis (TIVM).  The group agreed by a show of hands.

A new chair was elected by nomination and voting.  Thank you to all the people who were willing to assist the group by allowing their nominations to stand.  The new chair of the TIVM group is Carrie Valentine (cvalentine@nctr.fda.gov). JH will stay on as past-chair.  Barry Ford [barry_ford@hc-sc.gc.ca]volunteered to act as secretary for the coming year.

It was proposed that Dan Benz (EMS webmaster) be approached about providing some space on the EMS website and front end button to a page of links (including back issues of newsletters) relevant to the group. Members who have URLs (annotated please) which may be of interest to the group should forward these to BF, for inclusion on the web page.

Some points about the purpose of the group were discussed. THIS IS IMPORTANT.

It is agreed that the main thrust should be scientific discussions on real issues and/or real data, as opposed to business issues.  Business should not be the main work, and should be conducted as efficiently as possible.  It is also agreed that the group should treat presented data and discussions in confidence, in the vein of a "mini-Gordon conference".  Thus presenters should feel they can bring novel, preliminary, unpublished or controversial works to a receptive group of interested peers, without fear of being scooped or cited out of context. (secretary note: Newsletter reports will reflect this).  It was felt that such an approach would amplify the quality, value, and excitement value (at 7:00 in the morning!!) of our group meetings. This structure was accepted by general agreement.

Science Stuff :

Transgenic Mutation Assays

George Douglas [gdouglas@hc.sc.gc.ca] provoked some discussion on the question "Will transgenic mutation assays ever become part of regulatory requirements ?".  Various points were raised on areas of "insufficient agreement" (save that one), including :

• the need for regulatory guidelines
• discussion of treatment regimens
• the need to explain the purpose/need/advantages of TG tests in a regulatory context
• which endpoints ? :mutations (only?) : chromosome aberrations ? : other

GD also discussed an OECD Detailed Review, and solicited some contributions/assistance. 

A key point is to review existing in vivo tests to demonstrate gaps in current tools. People with messages to GD can send direct to him or via the secretary.

Presentations

(please contact the presenters directly for further information)

Don Ennis [dge5893@louisiana.edu] from Louisiana State presented a review of a direct selection system for Big Blue. This was in part an amplification of his poster from the meeting. In repsonse to some questions, Don submitted the following to the newsletter. For for more details, contact Don directly.

Briefly,we use a plasmid in the selection host that has lacO/P driving expression of the tetA gene, such that cells receiving a lacI+ gene on the phage shuttle vector ("lambda Liz") are Tet-sensitive.  Cells receiving a mutant that is lacI- fail to repress the tetA construct and hence are Tet-resistant.  The Amp resistance that I referred to in my little talk is on the lambda Liz phage vector. So in our system we can select for "lysogens" (actually phasmids) using Amp and select for lacI- mutants using Tet. Thus lacI- mutants are selected on plates with Tet and Amp. The question about Amp was related to the problem of satelite colonies.  We don't actually have a problem after overnight incubation with 100ug/ml, but begin to get annoying satelites colonies after several days incubation.

Asanga Halangoda [ahalangoda@coh.org] from Steve Sommer's lab at City of Hope presented some details from their poster, and provoked some discussion on sequence context and tissue influence of mutations.

Mugimane Manjanatha [mmanjanatha@nctr.fda.gov]  from the NCTR was the final presenter. The subject of Manju's talk was that when doing the Big Blue assay in bone marrow of the rat, the spontaneous background was ten times lower than normal, about 10e-6.  The induction of mutations above background by DMBA is 30-100-fold higher than this background: 100-fold at 140 mg/kg.   Therefore, this tissue provides the greatest sensitivity of any reported so far for Big Blue assays.(Thanks to CV for contributing these notes).

Some Useful Information :  Internet Sites on TIVM (a sampling)

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All submissions / suggestions considered.  email to  barry.ford@drdc-rddc.gc.ca