ACS Division of Chemical Toxicology

Newsletter

Editor, Katie Cottingham

In this Issue:

Message from Chair
2010 TOXI Travel Grants
Division of Chemical Toxicology Mission Statement: Why Revise?
Founders' Award Goes to Richard Loeppky
Quarterly Chemical Report: Acetaldehyde
Research Highlight: ACS Meeting Report
Career Corner: Writing Manuscripts, Part I
ACS National Meeting: TOXI Boston Program
TOXI Workshop for Young Investigators
TOXI Short Course at the National Medicinal Chemistry Symposium
How ACS Meeting Themes Are Chosen
Other Announcements

Message from the Chair, Professor Lisa A. Peterson

Lisa Peterson Despite the cold and snowy winter, there has been much activity within the Division of Chemical Toxicology. I have highlighted several of these activities below.

Strategic Plan. In January, the executive committee reviewed and approved the strategic plan. My thanks go out to the strategic planning committee for their development of the plan and to Tom Spratt, Pete Dedon, and Shana Sturla for their willingness to serve as leaders for the three major goals. These goals include:

Expanding active membership to include all relevant constituency groups;
Ensuring sustainable funding that will be adequate for TOXI activities; and
Having our expertise in chemical mechanisms for toxicology and disease processes recognized by ACS and its members, and using our expertise to advance the science and mission of the division. We have begun the work to accomplish these goals.

A major task of the strategic planning committee was to determine if our mission statement was in line with the current activities of the division. In an article below, Dan Liebler describes how the mission statement has been expanded to more accurately reflect the current state of the field of chemical toxicology.

In the near future, you will be asked to vote our updated bylaws which incorporate this expanded mission statement. Other changes include an increase in the term length for the nominations committee members, as well as the expansion of the treasurer's term to include a two year stint as treasurer-elect.

National ACS meeting in Boston, August 2010. You can submit your abstract for presentation at the Boston meeting now. The website will be open for submissions until April 2, 2010. The highlights of the scientific programming are outlined below. One new activity will be a workshop for young investigators on liquid chromatography-mass spectrometry and its applications. This workshop will be free to TOXI members. More details are given below. Thanks to Kaushik Mitra, Fred Guengerich, and the Professional Development Committee for putting together this exciting workshop. Information regarding workshop registration will be forthcoming.

National ACS meeting thematic programming. Based on some responses I had to previous newsletters regarding the national ACS meeting thematic programming, I have asked our Multidisciplinary Program Planning Group Division representative, Amanda Bryant-Friedrich, to explain how these themes are chosen and what their purpose is.

Travel Grants for Young Investigators. The Executive committee is pleased to announce two travel grants for students or postdoctoral associates to attend the meeting in Boston. More travel grants will be available if we are successful in obtaining funding from the NIH. Additional information regarding these travel grants is presented below.

Other Newsletter Highlights. Make sure you read the rest of the newsletter. There are many interesting contributions.

Don't miss the new installment of the Career Corner, a recurring column written by Peter Dedon. This column, which first appeared in the last newsletter and is the brainchild of Katie Cottingham, is an outstanding addition to our newsletter. Thanks, Pete and Katie!

I also want to thank Bob Carlson for his excellent assistance with the newsletter format.

Lisa

2010 TOXI Travel Grants

The Division of Chemical Toxicology (TOXI) will award travel grants to undergraduate and graduate students and postdoctoral researchers. Grants will be approximately $750 to reimburse travel and hotel costs for the ACS meeting in Boston this August (receipts will be required). Applications will be awarded on the basis of financial need, scientific merit, and diversity factors. All students and postdocs who are members or affiliates of TOXI and are interested in attending the National ACS meeting in Boston are eligible to apply. Note that if your meeting attendance is contingent on obtaining the award, but TOXI is unable to support your travel, it will be possible to withdraw your abstract at a later date. Details about the application process will be emailed to members.

Division of Chemical Toxicology Mission Statement: Why Revise?

by Daniel C. Liebler

At the Strategic Planning Retreat for the Division of Chemical Toxicology last August, the planning group discussed the need to revise the mission statement for Division. The previous version--a lengthy paragraph—is best represented by the concluding phrase:

"To increase the public welfare through an elucidation of the connection between chemical structure and biochemical action which results in toxic reactions."

We all agreed that this language inadequately represents the broader context for the work of TOXI scientists. Our colleagues study not only chemical toxicity per se, but also chemical mechanisms and biological processes that contribute to cancer, metabolic, and degenerative diseases. In many cases, the toxicities of exogenous compounds have direct parallels in endogenous pathologies. Indeed, most human diseases involve an interplay between environmental exposures and the effects of endogenous and exogenous chemical mediators. For these reasons, the planning group and the TOXI Executive Committee recommended a revised mission statement, which is concise and comprehensive:

"The mission of the Division of Chemical Toxicology is to improve human health and public welfare by promoting the understanding of chemical mechanisms that govern disease processes and the toxicity of drugs, environmental agents, and endogenous chemicals."

Members of the Division will recognize that TOXI programming at the annual meeting already represents these broad themes. The global program theme for the 2010 Fall National ACS Meeting is "Chemistry of Preventing and Combating Disease", which is well-matched to the focus articulated in the revised mission statement. TOXI will continue to expand along these themes through joint programming with other ACS divisions.

Finally, the Strategic Plan identified the need to secure recognition within the ACS for the unique expertise and scientific vision represented by our Division. Toxicology is often considered a somewhat narrow, specialized field that is separate from the mainstream of the health sciences enterprise. The revised TOXI mission statement explicitly places our discipline in a broadly significant human health context, where it belongs.

Founders' Award Goes to Richard Loeppky

by Kent S. Gates

It seems that Richard Loeppky was destined to become a chemist. His early interest in chemistry was spurred by the acquisition of a chemistry set and by a radio program called the "Cavalcade of America", sponsored by the DuPont Co., whose motto was "Better Things for Better Living Through Chemistry". He was also inspired by stories that his grandmother told him of how his distant relatives—the famous father and son Professors Silliman of Yale—discovered uses for Pennsylvania crude oil. In high school, his home laboratory experiments began to expand far beyond those suggested in his chemistry set as he figured out how to obtain or prepare more interesting chemicals, such as sulfuric acid, white phosphorus, and hydrogen gas.

After graduating from high school, Loeppky enrolled in the University of Idaho as a chemistry major. He spent the summers working in the same lumber mill where his father was employed. He recalls, "The work was hard and boring, but it paid very well and provided for my college education". He also remembers that the job "provided an additional impetus for me to obtain a degree and get out of town". His professors encouraged him to go to graduate school, and in the fall of 1959, Loeppky began his graduate studies at the University of Michigan. He joined the laboratory of Prof. Peter A. S. Smith where he examined the scope and mechanism of tertiary amine nitrosation reactions. Loeppky recalls telling his advisor over coffee shortly after his thesis defense that nitrosamines were boring compounds without much chemistry and that he probably would never return to this research area. Of course, neither prediction proved true. In 1963, he moved to the University of Illinois for an NIH postdoctoral fellowship with Prof. Nelson J. Leonard where he entered the field of purine chemistry, another subject that would resurface in Loeppky's independent work.

In 1964, when he was 26 years old, Loeppky accepted a professorial position in chemistry at the University of Missouri. Although he had not planned to reenter the field of nitrosamine chemistry, Loeppky gave a student an amine nitrosation problem, which he thought would be "surefire and short-term" project. The problem turned out to be much more complex and interesting than expected, however. These studies were followed by a fortuitous encounter at an ACS regional meeting in Lincoln, Nebraska with other researchers who were interested in the relevance of Loeppky's work to the generation of carcinogenic nitrosoamines from tertiary amines in vivo. These events set the stage for Loeppky's entry into the field of nitrosamine carcinogenesis. In the ensuing decades, Loeppky's group used the tools of mechanistic chemistry to shed light on carcinogenic N-nitroso compounds. His work centered on the definition of the bioactivation pathways of environmental and metabolically-generated ß-oxidized nitrosamines and the exploration of new nitrosation mechanisms for the generation of endogenous and exogenous nitrosamines.

Loeppky's research in the field of nitrosamine carcinogenesis led to his central role in conceiving and establishing the Division of Chemical Toxicology. In the early 1990s, he and others recognized that there was no appropriate venue for the presentation of work in this field. This led to the idea that chemical toxicology could be represented by a new division of ACS. Loeppky's dedication to the cause was substantial. He was instrumental in developing a petition, recruiting a leadership group and, most importantly, obtaining permission from various ACS committees and individuals to mount a drive for a new division. He also secured the approval of the existing ACS divisions and the ACS president. The division was granted probationary status and presented its first program at the Orlando meeting of the ACS in August 1996. Clearly, the Division has continued to flourish, and Loeppky has continued as an active participant in its leadership to this day. Please join me in congratulating Dick on his receipt of the Division of Chemical Toxicology's Founders' Award. This is a well-deserved honor.

Kent S. Gates is at the University of Missouri, Department of Chemistry.

Quarterly Chemical Report: Acetaldehyde

by Silvia Balbo

Acetaldehyde (AA) is a ubiquitous genotoxic compound that causes mutations, sister-chromatid exchanges, and chromosomal aberrations in cultured cells, and is also carcinogenic to rodents. Two major routes of exposure for humans are by inhalation and via the gastrointestinal tract. Smoking tobacco cigarettes represents a major inhalation exposure route, but humans also can be exposed via products of combustion such as vehicle emissions. AA is present in several foods, such as fruits, vegetables, and cooked meats. Gastrointestinal exposure also can occur when a person consumes alcoholic beverages. In the body, the ethanol in alcoholic drinks is metabolized to AA by alcohol dehydrogenase or cytochrome P4502E1. AA is then turned into acetate by acetaldehyde dehydrogenase (ALDH).

AA is a highly reactive electrophile that binds rapidly to DNA and cellular proteins, impairing cell functions. The formation of AA-related DNA adducts has been shown in various organs of alcohol-fed animals, as well as in leukocytes of alcoholics, suggesting that AA plays a key role in alcohol cancer-related pathways. The binding of AA to DNA resulting in the formation of stable adducts represents one of the mechanisms by which AA could trigger replication errors or mutations. N²-Ethylidenedeoxyguanosine is the major AA-derived DNA adduct. Levels of this adduct in DNA from human white blood cells and from rat livers were correlated with alcohol drinking, suggesting that it may be a useful biomarker of AA-related DNA damage.

In addition, polymorphisms or mutations in genes coding for AA detoxifying enzymes that result in increased AA concentrations are associated with increased cancer risk. The ALDH2*2 variant allele, which encodes an inactive enzyme, is prevalent in east-Asian populations (up to 30%). Heterozygous carriers who have ~10% activity accumulate acetaldehyde and have higher relative risk of alcohol-related esophageal cancer compared with individuals with more common alleles.

In light of these results, in October 2009, 30 scientists from 10 countries met at the International Agency for Research on Cancer (IARC) to reassess the carcinogenicity and identify additional tumor sites and mechanisms of carcinogenesis of several agents, including alcohol. The working group confirmed the Group 1 classification (carcinogenic to humans) of alcohol consumption and of ethanol in alcoholic beverages and also concluded that AA associated with alcoholic beverages is carcinogenic to humans.

Silvia Balbo is a postdoctoral fellow at the Masonic Cancer Center of the University of Minnesota. Her research interests include the investigation of effects of carcinogens present in tobacco products or formed from metabolism of ethanol after alcohol consumption. She is currently working on the development of methods to analyze carcinogen metabolites in urine and carcinogen DNA adducts in tissue or blood.

Research Highlight: ACS Meeting Report

by Jason Berninger

Jason Berninger Attending the American Chemical Society Meeting, and specifically the Division of Chemical Toxicity sessions, provided me with several opportunities for professional development. The ACS-TOXI session was one of the first opportunities I have had to present results to a broad audience at a national meeting. By speaking at a national conference in front of a group of learned peers, I was able to hone my oral presentation skills. The presentation was also helpful professionally because it allowed my research to reach a wider audience, disseminating my ideas and concepts in a manner in which their merits could be discussed and debated.

By meeting and interacting with colleagues, the TOXI sessions also helped me expand my professional network. As a graduate student, developing a network of professional contacts is important both for my research and for my future career. Although I was not actively seeking a job, the opportunity to meet, discuss, and interact with scientists beyond my university allowed me to get to know potential employers.

There was a lot to learn during the TOXI sessions. It was very interesting to learn about the exciting research that other people have done. It was also good to see some people present opposing viewpoints. Often, as researchers, we are so involved in our own hypotheses that we do not consider the opposite point of view. This meeting gave me an opportunity to see the scientific merits of alternative arguments. Also, by listening to the other speakers in my session, I learned of some potentially important sources of data and other resources of which I was not aware. Lastly, by being at the meeting, I was able to integrate concepts and new testing methodologies in order to further my own research.

I spent the most time attending the session at which I was a speaker: "Advances in Aquatic Toxicology: Alternative Nontraditional Endpoints". I really benefited from listening to the other talks because they provided viewpoints and perspectives different from my own. Also of great interest was the discussion at the end of the session, which included all of the speakers and the audience members. Being involved in professional discourse and debate on my topic of interest really gave me confidence in my research and development path as a graduate student.

The TOXI grant allowed me to attend this meeting. As a graduate student receiving a departmental stipend, fiscal responsibility is paramount. This can mean that expenses, personal and professional, come at a cost to other activities, such as travel. By seeking funding from external sources, like the TOXI travel grants, I can take advantage of the opportunities that come with attending and presenting at scientific conferences. I benefited professionally from attending the ACS Chemical Toxicity conference without having to struggle financially.

Overall, this was a great meeting. I was able to present my research to a wide audience, hone my presentation skills, and further develop my professional network. The sessions were well done, and I learned a lot of new and exciting science.

Jason Berninger was awarded a 2009 TOXI Young Investigators Travel Grant. He is a graduate student at Baylor University in Waco, Texas.

Career Corner: Writing Manuscripts
Part I: Strategic Planning

by Peter Dedon

Peter Dedon The previous Career Corner was devoted to scientific presentations, a topic that naturally leads to another means of communicating our scientific observations: writing manuscripts for publication. Just as with public presentations, manuscript writing must achieve the objective of communicating your complicated observations and results to a diverse audience, while convincing the broader scientific community of the importance, impact and rigor of your work. Indeed, the number and quality of your publications often serves as a barometer of your professional or scholarly achievement, with serious implications for job applications and promotions.

The next two Career Corner contributions will explore manuscript preparation, with an emphasis on hypothesis-driven or methods-oriented biomedical science. I will not address the mechanics of preparing a manuscript—font size, organization, abbreviations and supplementary materials—which are journal-dependent and spelled out in the instructions to authors on every journal's web site. Instead, we will explore the more subtle aspects of writing a paper, such as creating the perfect title, structuring the logical flow of ideas, organizing the results and discussion sections and the importance of a good materials and methods section.

Entire careers and Ph.D. theses have focused on the art of scientific writing and communication, but we can boil the manuscript process down to two phases, which we will address in this and the next Career Corner: strategic planning and the writing itself. Strategic planning is the equivalent of sketching the broad outlines of the manuscript. The goals are to:

define the main conclusions and the "take-home messages" of your studies;
choose the appropriate audience and journal for those messages; and
identify three or four "talking points" raised by the results.

The actual writing process develops the logical flow of ideas leading to the conclusions, and we will cover strategies for construction of the introduction, results, discussion, materials and methods, abstract and title in Part II. I have found this order to be a natural progression in writing, with the challenge of summarizing complicated work as an abstract saved until all of the concepts have been fully developed in the main body of the manuscript.