Editor, Shana Sturla
In this Issue:
Message from the Chair
Message from the Division Chair, Professor Lisa A. Peterson
 I would like to open my first newsletter as Chair of TOXI with a few thank you's. First of all, I would like to thank Fred Guengerich for his outstanding leadership during the past two years as Chair. We are positioned for a bright future as a result of his many efforts. He leaves big footprints to follow in. I would also like to thank Kent Gates for his service as Program Chair for the past two years. He did a fantastic job, providing strong programming during his tenure. His able successor, Kashik Mitra, will continue in the tradition of outstanding TOXI program officers. Another BIG thank you to Dick Loeppky for his many years as newsletter editor. Dick has performed a tremendous service to the division through this role. I look forward to working with his successor, Shana Sturla. I would like to thank the nominating committee (Judy Bolton, Paul Hollenberg and Larry Keefer) for putting together a strong slate of candidates for the fall elections. I also thank all those who were willing to run for the elected positions. I think it speaks well of our division that we have so many capable individuals willing to serve this division in so many different capacities. My congratulations to those elected. I look forward to working with all of you in the years ahead. Thanks to Tom Spratt for setting up and executing our first electronic election.
2009 is off to a great start. The finance committee chaired by Pete Dedon has already met by telephone to plan their strategy for our 2009 fundraising effort. The short course committee, chaired by Griff Humphreys, has organized a course entitled "Chemical Toxicology: A Chemist's Roadmap to Reduce Bioactivation Liabilities in Drug Candidates" that will be presented at both National Meetings this year. In addition, we are beginning to organize our ACS-facilitated strategic planning process. More details about this will be forthcoming.
As outlined below, Kaushik Mitra has put together a strong and interesting scientific program for the August ACS meeting of the division in Washington DC. The call for abstracts has gone out with a deadline of March 15. We look forward to receiving your abstract. The contributed papers are an important part of our programming each year.
Congratulations to Steve Hecht, the 2009 recipient of the Founders' Award! This award was established by the Division to honor the vision and contributions of individuals who worked to get to the division started in the mid-1990s. The Founder's award recognizes TOXI members for their outstanding contributions to chemical toxicological research. An account of Steve's contributions to the field appears below.
ACS is launching an ACS fellows program this year. Our division may nominate up to four individuals for this honor. The executive committee has established an awards committee to facilitate the nominations process. This committee will be chaired by Dan Liebler, Chair-elect. Please forward him any nominations for this prestigious program (dan.liebler@vanderbilt.edu). The ACS deadline for nominations is April 15, 2009 so we will need your nominations before April first
In closing, I encourage you to contact me or any member of the executive committee with your thoughts on how we can make our great division even stronger.
Lisa
Stephen Hecht Wins 2009 Founders Award
Heralded researcher hits the streets in hard times
By Richard Loeppky
 When you look at the curriculum vita of Stephen Hecht, this year's founders Award winner, you have to wonder how he ever got from a small college teaching job to a position where he has made phenomenal contributions to knowledge of the chemistry of carcinogenesis, and to the reduction and prevention of tobacco-related cancers. He is the most cited and published researcher in the field of tobacco carcinogenesis. Steve points out that when he left MIT in the late 1960's the employment situation for chemists was poor, as it is today. Armed with an honors degree from Duke, a Ph.D. in organic chemistry from MIT (Profs. Cope & Greene), a postdoc in mass spec (Prof. Biemann, MIT) and a passion for organic chemistry, Steve hit the streets looking for a job. All he could find was a temporary teaching job at Haverford College in the Philadelphia area. After two years the job situation was still bleak, but he did get a position as NRC Fellow at the Regional USDA laboratory in Philadelphia. Remarkably, this led him to the then fledgling American Health Foundation in New York where he was recruited by Dietrich Hoffmann to work in the area of tobacco carcinogenesis. Soon after Hecht began working on both polycyclic aromatic hydrocarbons, and nitrosamines. Hecht told Hoffman's that his goal was to do good chemistry. N-nitrosonornicotine (NNN) was found to be a constituent of both tobacco smoke and cured tobacco and Hoffman was looking for an improved way to get more NNN. He told Hecht to nitrosate nicotine, a tertiary amine. The results of this experiment were to have landmark consequences in the field of chemical carcinogenesis (see sidebar). Using published work on the mechanism of the tertiary amine nitrosation as a guide, along with his MS acumen, Hecht showed that among the many products and NNN, another nitrosamine NNK was a major product of this transformation. Hecht and his collaborators quickly went on to show that NNK was a potent lung carcinogen in experimental animals, and also revealed is presence in tobacco and tobacco smoke. Mechanisms of its formation in curing and smoking tobacco were elucidated and modes of carcinogen level reduction explored. However, determining actual human exposure remained problematic at this stage.
Although he had never taken a college level biology course, and had only one biochemistry course as a graduate student, Steve realized from the work of the Elizabeth and Jim Miller, Alan Conney, and Don Jerina that it was important to establish the bioactivation mechanism for these new nitrosamines. Guided by Peter Magee's pioneering and seminal research on the bioactivation and nucleic acid binding dimethylnitrosamine, Hecht and his collaborators went back to the lab and made -acetates and nitrosourethanes that were expected to hydrolyze to the same reactive intermediates expected from enzymatic activation of N-nitrosopyrrolidine and NNN. They identified decomposition products, developed sensitive analytical methods for these substances and then sought to determine whether they were urinary metabolites in whole animal experiments. Before long they had elucidated a complete metabolic profile for NPYR, NNN, NNK and its important bio-reduction product NNAL. As the research expanded, many of the DNA and protein adducts produced from the reactive metabolites were identified, synthesized, and developed as biomarkers, first in experimental animals and then in humans. At the same time Hecht used these same paradigms in his tobacco-related PAH research.
Hecht believes that the chemical biomarkers are tremendously important in the quest to reduce cancer incidence. With his colleagues, he has designed and participated in many important epidemiological studies. A recent prospective study shows that NNAL is the only statistically significant biomarker of human lung cancer. Hecht's work in this vein has led to the designation of NNK and NNN as human carcinogens by the IARC, a rare designation. His group has also explored the mechanisms and effectiveness of several vegetable borne anticarcinogens. In all of this multifaceted research, Hecht cites that which has involved and evolved from the NNK work as the most significant.
Steve Hecht is a passionate advocate of the importance of chemical and biochemical mechanistic studies not only in chemical toxicology and cancer research, but also in investigations of the pathogenesis of other diseases. All of his very successful biomarker research evolved from these challenging, but very rewarding mechanistic studies. He points to the importance of understanding metabolic activation and to the very significant contributions of others in the chemical toxicology community. He believes there is a world of opportunity for young scientists in this area. Yet he is concerned that young investigators perceive cancer research and like endeavors as biology and do not realize the potential of chemical toxicology. He advises the young investigator to stand by their main hypotheses and not be distracted by every new fad. " Keep your eye on the big picture, but be attentive to the detail of your results. Good science is built on those details," he advises
As recipient of TOXI's second annual Founder's Award Hecht is being recognized for his exceptional research and accomplishments in chemical toxicology, tobacco carcinogenesis, and cancer prevention through chemistry. The award is given to a TOXI member whose scientific activities have emphasized innovative research in the general field of chemical toxicology. Steve was also the second chair of TOXI and was involved in the division's organization. Some of his research accomplishments are highlighted in the sidebar. Last year, the first Founders' Award was given to Larry Marnett.
Dr. Stephen S. Hecht is Professor of Medicinal Chemistry and Wallin Land Grant Professor of Cancer Prevention and Professor, Department of Laboratory Medicine and Pathology at the University of Minnesota. He is married to Dr. Sharon Murphy, an outstanding biochemistry professor at the University of Minnesota. They have two daughters
Richard Loeppky is Professor Emeritus of the Department of Chemistry at the University of Missouri. Richard Loeppky is a longstanding researcher in the field of nitrosamine chemistry and carcinogenesis, and has known Stephen Hecht for many years. Loeppky was the first Chair of TOXI and organized the Division with Steve Hecht, Larry Marnett, Lisa Peterson and others. He is Professor Emeritus, Department of Chemistry at the University of Missouri and a Faculty Affiliate in the Department of Medicinal Chemistry at the University of Washington, Seattle.
 Chem Tox Wiki
By Martin Phillips
Who is Cynna Kydd? What is the history of the board game Monopoly? What is Chemical Toxicology and why is it important? Like many questions that students and the general public have today, they may find answers with a wiki search. Searching Wikipedia for the first two questions, one would find a comprehensive and well-referenced collaboratively developed article. Unfortunately, not the case for Chemical Toxicology.
What is a wiki? A wiki is a website where the pages may be edited online by anyone with access to the page. Wikis are usually edited using a simplified computer language and without special software. Wikipedia is the most widely used wiki. The site was originally launched on January 15, 2001 and has since then exploded in popularity. There are currently more than 2,722,000 Wikipedia articles in English alone, and there are articles in 253 languages. Tracking results suggest Wikipedia is the 8th most visited site on the entire internet.
Almost all articles may be anonymously edited by anyone. Only registered users may create new articles. Some articles are frequent targets for vandalism, where the content is deliberately changed to be false, misleading, or humorous, and these articles are locked. Locked articles may only be edited by registered users, and some may only be edited by administrators (volunteers who provide expertise on a topic and are frequent contributors to the encyclopedia). Registration is fast and free, but it allows administrators to track what changes a user is making and ban them if they are vandalizing the website. The Wikimedia Foundation, a 501(c)(3) nonprofit corporation, manages Wikipedia.
The accuracy of Wikipedia has been frequently called into question. Good articles cite their references at the bottom of the page and usually have a large number of hyperlinks to similar topics within Wikipedia. The fact that so many users may edit an article means that mistakes are often corrected as quickly as they are made. Administrators and specialized computer programs (called bots) also correct errors quickly. The history function (found at the top of each article) allows edits to be tracked and historical versions to be compared to one another.
The Chemical Toxicology Page
Chemical toxicology is currently covered in Wikipedia only briefly under the general toxicology article [en.wikipedia.org/wiki/Toxicology]. To enhance this potential portal to chemical toxicology, our goal is to expand coverage of this important area so that it will have its own page. Examples of information that might be included are: the history of chemical toxicology, typical problems that chemical toxicologists study, the methods and instrumentation employed by a chemical toxicologist, how chemical toxicology fits into the broader discipline of toxicology and ultimately into public health and medicine, the education of a chemical toxicologists (examples of coursework, schools that specialize in the field, important textbooks/reference books, etc), different career paths and employment opportunities for chemical toxicologists, subdisciplines within chemical toxicology, and peer-reviewed scientific journals where chemical toxicologists publish their research. As members of the ACS Division of Chemical Toxicology, we are uniquely qualified to accurately update the Chemical Toxicology page. Simple instructions for creating and editing Chemical Toxicology information on Wikipedia can be found by clicking here and downloading a pdf. As a graduate student beginning my research career and using Wikipedia, I can raise the level of generally accessible information available on the internet in a field that I think is extremely important, and hope you will join me. I'll update you on our progress in an upcoming newsletter. Good luck, and have fun!
Martin Phillips is a graduate student at the University of Minnesota, Minneapolis, MN. After obtaining a B.S. in Chemical Engineering, he is pursuing a Ph.D. in Medicinal Chemistry with a minor in Toxicology. He is a member of Lisa Peterson's laboratory and has research interests in the area of furan carcinogenesis.
Quarterly chemical Report: 4-Hydroxy-2-nonenal
By Jonathan A. Dorn
 4-Hydroxy-2-nonenal (4HNE) is an α,β-unsaturated aldehyde found to be a major product of lipid peroxidation. Specifically, the lipid aldehyde results from oxidation of ?ω-6 polyunsaturated fatty acids such as linoleic and arachidonic acid, and low, sub-µM levels of 4HNE exist under basal conditions; however, the concentration may greatly increase during oxidative stress, especially when cellular defenses are overwhelmed. Therefore, 4HNE is often regarded as a biomarker for oxidative stress. Since the discovery of the lipid aldehyde several decades ago, numerous reports have been published implicating a role for 4HNE in a myriad of human diseases, such as atherosclerosis, cancer and neurodegenerative diseases (i.e., Parkinson's, Alzheimer's). 4HNE is an insidious species, toxic to cells and highly reactive toward cellular nucleophiles. The α,β-unsaturated aldehyde moiety is considered to be a soft electrophile given the presence of the oxygen adjacent to the alkene, which can polarize the pi electrons in this conjugated system. Numerous studies have demonstrated DNA bases and protein residues to be targets of 4HNE. In particular, the guanine base is susceptible toward modification, yielding a cyclic adduct. Protein residues, such as Cys, His and Lys, readily react with 4HNE at the C3 position via Michael-type addition, yielding an adduct that rapidly rearranges to a cyclic hemiacetal. Metabolism of the lipid aldehyde can occur via various pathways, including aldehyde oxidation, catalyzed by aldehyde dehydrogenases, and reduction, resulting from several reductases (e.g. aldose-keto reductases). In addition, conjugation with glutathione represents a major component to 4HNE detoxication. Reaction of glutathione with the lipid aldehyde is spontaneous and occurs rapidly but can be catalyzed by glutathione-S-transferase. Given the high reactivity of 4HNE (e.g., glutathione), the estimated half-life for this molecule under physiologic conditions is short and in the range of minutes. Current research on this exciting and important molecule is focused on identifying specific targets of 4HNE (e.g., proteins, signaling pathways) and elucidating the role of this reactive aldehyde in toxicity and disease.
Jonathan A. Doorn, Ph.D. is Assistant Professor of Medicinal and Natural Products Chemistry at the University of Iowa. A major focus of his research concerns reactive intermediates of dopamine metabolism and their role in neurodegenerative disease, and he has a long-standing interest in understanding the role of metabolism in 4HNE toxicity.
Chemical Toxicology Upcoming Events and Requests Round-Up
Call for Papers at the Fall ACS Meeting:
March 15 ABSTRACT SUBMISSION DEADLINE
Technical Programming at the Washington DC ACS meeting will target a variety of academic and industrial interests, highlighting new facets of chemical toxicology.
- Founders' Award Symposium
in honor of Stephen S. Hecht
- Advances in Aquatic Toxicology: Alternative Non-traditional Endpoints
organized by Bryan Brooks and Richard Brain
- Human Drug Metabolites in Safety Testing: Guidelines & Strategies
organized by Fred Guengerich
- Drug-Induced Mitochondrial Dysfunction and Human Disease: New Insights and Applications
organized by Kevin Leach and David Thompson
- DNA Adducts and Human Health
organized by Paul Henderson
- Platinum-based Chemotherapeutics: New Approaches for Cancer Treatment
organized by Paul Henderson
In addition, there will be three sessions providing opportunities for submitted abstracts in all areas of chemical toxicology: general oral presentations, oral presentations by young investigators (graduate students and post-docs), and general poster presentations. As every year, the oral and poster presentations by graduate students and post-docs would be entered, if the presenter is so willing, into a competition judged by an esteemed panel of academic and industrial scientists. Winners will receive a plaque and monetary award.
- General Papers, Oral Presentations
organized by Kaushik Mitra
- Young Investigators, Oral Presentations
organized by Kaushik Mitra and Shana Sturla
- General Papers, Poster Presentations
organized by Kaushik Mitra
Authors wishing to make presentations at the Washington DC ACS Meeting (August 16-20, 2009) are reminded that the deadline for submission is
12:00 AM Monday, March 16th .
Sunday March 15 will be the last day to submit abstracts
To submit an abstract, go to the OASys website http://oasys.acs.org/, scroll down to the TOXI link and follow the instructions for abstract submission.
View a short QUICKTIME VIDEO of the Chemical Toxicology Programming at the 2008 ACS Meeting in Philadelphia
Chemical Toxicology Short courses
The ACS has two short-courses lead by by members of the Chemical Toxicology Divisions. The first offerings will be at the ACS Spring national Meeting in Salt Lake City. The registration deadlines are coming soon, so sign up.
Short Courses are an excellent way keep current in today's competitive marketplace. Attendees find the content of these courses contain a wealth of material that is immediately applicable to their work.
Chemical Toxicology: A Chemist’s Roadmap to Reduce Bioactivation Liabilities in Drug Candidates , led by instructors Fred Guengerich, Kaushik Mitra, Christine Fandozzi, and Griff Humphreys, will run March 21, 2009 in conjunction with the ACS Spring National Meeting in Salt Lake City, UT.More Info
Introduction to Drug Metabolism: Role and Practice in Drug Discovery and Development , taught by Drs. Donglu Zhang and Mingshe Zhu, will run March 22, 2009 also in conjunction with the ACS Spring National Meeting in Salt Lake City, UT.
Early registration and group discounts are available. Visit our website for complete details.
Call for TOXI Nominees to ACS Fellows Program
The ACS Fellows Program recognizes members of the American Chemical Society for outstanding achievements in and contributions to Science, the Profession, and the Society. The distinguished honor of a Fellows designation will go to those who have distinguished themselves in multiple areas, including promoting the science, the profession, and service to the American Chemical Society. The selection of Fellows will be based upon excellent contributions in two defined areas:
- Excellence in Science/Profession which could be achieved via excellence in basic or applied research; distinguished accomplishment in teaching or education; or demonstrated leadership or managerial excellence in an organization within the chemical sciences; and
- Outstanding Service to the ACS which could include, but not limited to, governance on a divisional, local, regional and/or national level; publications such as editor, assistant or associate editor; meetings through organization of symposia or major presentations; involvement in National Chemistry Week, Chemists Celebrate Earth Day, environmental efforts and similar outreach activities or public communication by press, radio, TV or electronic media.
Nominate deserving members of TOXI by contacting the chair of the TOXI-ACS Fellows Nomination Committee, Professor Daniel Liebler (daniel.liebler@vanderbilt.edu.), before the April 15 ACS nomination deadline. Additional information on the ACS Fellows Program can be obtained in the "ACS Comment" in the Jan 19 issue of C&EN by Dr. Bruce E. Bursten, Immediate Past President, and by email to: fellows@acs.org
Chemical Toxicology Positions
Remember to check the Chem Tox Website at www.acschemtox.org/jobs/index.htm for job opportunity announcements. There are crrently several post-doctoral opportunities availableimmediately. Employers: Email any openings to Tom Spratt at tes13@psu.edu
ACS-WIDE NEWS AND ANNOUNCEMENTS
Former ACS President Bursten Praises House Speaker's Support for Science
Bruce Bursten, Ph.D., immediate past president of ACS, has praised U.S. House Speaker Nancy Pelosi for her promise that science will be of major importance in the upcoming Congress.
Leaders of major institutions representing government, academia, business and science were invited to attend the Innovation Roundtable hosted by House Speaker Nancy Pelosi at Princeton University last December.
In his remarks to the gathering, Dr. Bursten said "Science and engineering must be the engines of the innovation that assure our economic prosperity, our national security, our energy independence, and our responsible stewardship of our planet." Dr. Bursten is Dean of the College of Arts and Sciences at the University of Tennessee, Knoxville.
The purpose of the annual roundtable was to discuss how Congress could move ahead to renew the national commitment to the physical sciences and energy research.
ACS Mini-Grants Available for Collaborative Activities
Proposals are being sought for Equipping the 2015 Chemical Technology Workforce mini-grants. Up to $500 will be awarded to collaborative activities that support technician education and career development.
Equipping the 2015 Chemical Technology Workforce has three goals:
- Raise awareness of the changing needs of chemical technicians, operators, analysts, and other applied chemical professionals.
- Highlight opportunities for industry, academia, professional societies, and the community to collaborate on meeting those needs
- Increase involvement of applied chemical professionals in the American Chemical Society
To qualify for a mini-grant, one or more sectors of the chemical enterprise (industry, academia, professional organizations, etc.) must collaborate on the activity. Activities must also support one or more of the goals of Equipping the 2015 Chemical Technology Workforce and take place in the 2009 calendar year.
The deadline for proposals is 20 February 2009.
To learn more about Equipping the 2015 Chemical Technology Workforce and the mini-grants, to get ideas for activities, or to gather information about the chemical technology profession in today's marketplace, please visit the Equipping the 2015 Chemical Technology Workforce website (go to www.acs.org and follow the path, Funding & Awards > Grants > Chemical Technology Partnership).
ACS Spring Regional Meetings
The 2009 Regional Meetings are online and planning their programs. All three of the spring meetings will have programming pertaining to the environment, and GLRM and CERMACS have planned their meetings around an environmental theme. Plans are underway to open their abstract programs and advance registration in the immediate future.
The Great Lakes Regional Meeting (GLRM), http://www.glrm2009.org/ will take place in Lincolnshire, IL, just outside Chicago, May 13 - 16. Their theme is "A Better Environment through Chemistry." Symposia planned include plant biochemistry, material science/polymer chemistry, ethics in college education, non-crystalline x-ray structural chemistry and the environment, and molecular simulation in and for the environment.
The Central Regional Meeting (CERMACS), hosted by the Cleveland Section, which will be celebrating its 100th anniversary. Mark the dates, May 20 -23, and visit their website at http://www.case.edu/cermacs/ for details. Their theme is "Meeting Energy and Environmental Challenges through Functional Materials." Four other societies will co-sponsor and submit programming to CERMACS. They are the Electrochemical Society, Society for Applied Spectroscopy, American Vacuum Society, and the Yeager Center for Electrochemical Science. Case Western Reserve University also is a contributor.
The Northwest Regional Meeting (NORM) will take place June 28 - July 1 at Pacific Lutheran University, Tacoma, WA. Visit their website at http://www.chem.plu.edu/norm2009/ for information on their plans. Included in their program are sessions on bioanalytical mass spectrometry, chemistry of the bioregion; chemistry, energy, and sustainability; clinical chemistry, and instruments for the teaching laboratory.
ACS Short Courses in 2009
ACS Short Courses are one- to five-day, in-person seminars designed to help chemical scientists and technicians keep current in today's competitive marketplace. Please visit www.acs.org/shortcourses to register and for more information.
Short Courses at the ACS National Meetings
Going to an ACS National Meeting? Short Courses are held at each National Meeting and offers the opportunity to take advantage of a wide range of course offerings before and during the meeting.
March 21 - 26, 2009 | Salt Lake City, UT - ACS Spring National Meeting
Courses in Organic Chemistry, Chemical Engineering, Management, Cheminformatics, Spectroscopy, Polymer Chemistry, Intellectual Property, and Toxicology
Laboratory/Lecture Courses
Get in-class and hands-on experience with Laboratory/Lecture Courses from the ACS.
March 30 - April 3; July 13 - 17; October 5 - 9 | Chicago, IL
High Performance Liquid Chromatography: Fundamentals, Troubleshooting, and Method Development
April 20 - 24; July 20 - 24, November 9 - 13; | Chicago, IL
Gas Chromatography: Fundamentals, Troubleshooting, and Method Development
March 15 - 20; August 9 - 14; December 6 - 11 | Virginia Tech, Blacksburg, VA
Polymer Chemistry: Principles and Practice
Try out an ACS Webcast! It's easy and economical.
ACS offers a wide variety of webcast short courses and our winter/spring schedule is open for registration now.
There are expanded course offerings in analytical, organic, pharmacology, engineering, instrumentation, and other areas. For the full list of Webcast Short Courses and more information on available discounts, visit www.acs.org/webcourses
For more information visit the ACS Web Site.
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