ENVR 442 / TOXC 442 / BIOC 442

BIOCHEMICAL AND MOLECULAR TOXICOLOGY

Fall 2009

3 credit hours

3:30-4:45, Tuesdays & Thursdays

0003 Hooker Research Center

 


PREREQUISITES

Any combination of two courses in biochemistry, molecular biology, cell biology, or cell physiology (or permission of course director).

FACULTY

Ivan Rusyn (Course director)

0031 Hooker Research Center

iir@unc.edu

Louise M. Ball

158 Rosenau

lmball@unc.edu

Phil Smith

1317 Kerr

pcs@email.unc.edu

Kim Brouwer

3205 Kerr

kbrouwer@unc.edu

David Threadgill

NCSU

threadgill@ncsu.edu

Stephen Ferguson

CellzDirect, Inc.

Stephen.Ferguson@lifetech.com

Rebecca Fry

0032 Hooker

rfry@unc.edu

Thomas O’Connell

The Hamner

tom_oconnell@med.unc.edu

Igor Pogribny

NCTR/FDA

IPogribny@nctr.fda.gov

David Dix

US EPA

Dix.David@epamail.epa.gov

James Swenberg

2002 Hooker

james swenberg@unc.edu



COURSE PURPOSE
This course is designed for graduate and advanced undergraduate students in Environmental Sciences & Engineering, Toxicology, and related disciplines. The completion of a Human Genome Project has significant implications for molecular biology, genetics, medicine, and environmental sciences and toxicology. New experimental techniques that are based on a better understanding of genes and their actions rapidly proliferate into laboratories; thus, the students need to have a broad knowledge of metabolism, mechanisms and effects of toxicants, as well as to understand techniques that are available for their laboratory research. To achieve these goals, the material that is to be covered in this course spans from basics of biochemical processes that are affected by environmental agents, to molecular mechanisms of action, and to current experimental approaches in environmental sciences and toxicology.


COURSE DESCRIPTION
This course will consist of lectures, in-class discussions and periodic examinations. The overall emphasis will be made on biochemical and molecular actions of toxicants and assessment of cellular and molecular effects. The students are expected to develop a comprehensive understanding of biochemical and molecular changes caused by environmental chemicals and toxicants.


CLASS SCHEDULE

1

Tuesday, August 25, 2009

I. Rusyn

Overview of the science of toxicology

2

Thursday, August 27, 2009 

L. Ball

Metabolism of xenobiotics I (general overview); TCDDLancet; TCDDExperientiaPoiger 

 

 

 

 

3

Tuesday, September 1, 2009

L. Ball

Metabolism of xenobiotics II (phase 1 metabolism); GrapefruitPayneJPET; Guengerich_2008

4

Thursday, September 3, 2009

P. Smith

Metabolism of xenobiotics III (phase 2 metabolism); UGT Lecture,9.2009; Testa,Review,2008

 

 

 

 

5

Tuesday, September 8, 2009

K. Brouwer

Metabolism of xenobiotics IV (transporters); Chandra_Brouwer_2004; Klaassen_2008

6

Thursday, September 10, 2009

S. Ferguson

Induction of metabolism by toxicants; Goodwin1999; Jonesetal 2003; Wang 2003

 

 

 

 

7

Tuesday, September 15, 2009

G. Pollack

Toxicokinetics and toxicodynamics

8

Thursday, September 17, 2009 

I. Rusyn 

 Model systems and organisms in toxicology; Dambach 2005 ; Collins 2008

 

 

 

 

9

Tuesday, September 22, 2009

D. Threadgill

Rodent models in toxicology

 

Thursday, September 24, 2009 

Examination I (in class)

 

 

 

 

10

Tuesday, September 29, 2009 

I. Rusyn 

Biomarkers of toxicity ; Goodsaid et al 2008; NTP Biomarkers Workshop 2006

11

Thursday, October 1, 2009 

I. Rusyn 

Reactive oxygen species; Kensler 2007; Antioxidant enzymes and functions

12

Tuesday, October 6, 2009  

I. Rusyn 

13

Thursday, October 8, 2009 

R. Fry

DNA damage and repair

 

 

 

 

14

Tuesday, October 13, 2009  

I. Rusyn  

Mechanisms of cell poliferation

15

Thursday, October 15, 2009  

I. Rusyn   

Mechanisms of cell death ; Galluzzi_et_al_2009; Mercer_2007

 

 

 

 

16

Tuesday, October 20, 2009  

I. Pogribny

Role of epigenetic events in responses to toxic agents; Baccarelli_CurrOpinPediatr_2009

 

 

 

 

17

Tuesday, October 27, 2009  

I. Rusyn    

Chemical-induced carcinogenesis ; NTP levels of evidence; Nebert & Dalton 2006

18

Thursday, October 29, 2009  

I. Rusyn    

Role of genetic polymorphisms in responses to toxic agents; Walko & McLeod 2009; Frueh et al 2008

 

 

 

 

Tuesday, November 3, 2009

   Examination II (in class)

19

Thursday, November 5, 2009 

D. Dix

Toxic effects of pesticides 

 

 

 

 

20

Tuesday, November 10, 2009  

I. Rusyn

Toxic effects of inorganic salts

21

Thursday, November 12, 2009  

I. Rusyn

Toxic effects of hydrocarbons and alcohols 

 

 

 

 

22

Tuesday, November 17, 2009   

I. Rusyn 

 Gene expression profiling in toxicology; Frueh 2006; Dix et al 2006

23

Thursday, November 19, 2009  

I. Rusyn 

Proteomics applications in toxicology

 

 

 

 

24

Tuesday, November 24, 2009    

T. O’Connel 

 Metabolomics applications in toxicology

 

 

 

 

25

Tuesday, December 1, 2009

D. Dix

Computational toxicology

26

Thursday, December 3, 2009  

J. Swenberg

Molecular dosimetry 1-2

 

 

 

27

Tuesday, December 8, 2009

J. Swenberg

 

 

 

 

 

Tuesday, December 15, 2009

   Examination III (in class)

 

Thursday, December 17, 2009   

Take home Final Exam is due

ENVR 442 2009 Final exam guide

He_et_al_2009

Li_et_al_2009

Rakhshandehroo_et_al_2009

Reisman_et_al_2009


GRADES

Grades will be based on three in-class examinations and one final take home, open book examination. Active student participation in the course is strongly encouraged.

In-class Examinations:  ( I-III ) will test knowledge, comprehension, application, analysis, and synthesis (see definitions from the UNC Center for Teaching and Learning below). Each exam will be based on preceding lectures:
Examination I - lectures 1 through 9
Examination II - lectures 10 through 17
Examination III - lectures 18 through 27
Each examination will have 10 to 15 questions (predominantly of a very short essay type) and the maximum score will be 60 points, or 20% of the course total.  The students may not use reference materials, lecture notes or other aides during in-class examinations. Exams are not rescheduled unless pre-approval from a course director is granted in advance.

Knowledge: the recall of specifics and universals, involving little more than bringing to mind the appropriate material. The student recalls or recognizes information, ideas, and principles in the approximate form in which they were learned.

Comprehension: the ability to process knowledge on a low level such that the knowledge can be reproduced or communicated without verbatim repetition. The student translates, comprehends, or interprets information based on prior learning.

Application: the use of abstraction in concrete situations. The student selects, transfers, and uses data and principles to complete the problem or task with a minimum of direction.

Analysis: the breakdown of a situation into its component parts. The student distinguishes, classifieds, and relates the assumptions, hypotheses, evidence, or structure of a communication or concept.

Synthesis: the putting together of elements and parts to form a whole. The student originates, integrates, and combines ideas into a product, plan or proposal that is new to him or her.


Final Examination:  will test all skills detailed above plus evaluation ability. The materials for the final exam will be distributed in September/October along with a list of questions. The students will be asked to review and critique a published manuscript that describes the use of novel molecular biology technique(s) in studies of the mechanisms of action of environmental chemicals. The use of textbooks, lecture notes and other appropriate material is encouraged. The maximum score for this exam is 105 points, or 35% of the course total.

Evaluation: the making of judgments about the value of material/methods. The student appraises, assesses, or critiques something on the basis of specific standards and criteria.

Participation: the students are encouraged to attend all lectures and actively participate in class discussions. The maximum score for participation is 15 points, or 5% of the course total.

Grading: will be based on the following criteria adjusted to the overall performance of all students taking the course this semester after summation of all points as detailed above:

At least 90% of the Maximum score ( “H-to-P cutoff”)

H

At least 80% of the Median score (“P-to-L cutoff”) but less than 90% of the maximum score

P

Between 70% and 79.99% of the Median score (“L-to-F cutoff”)

L

Below 70% of the Median score

F


READING MATERIALS

The students are encouraged to review class handouts prior to each lecture by downloading the material from the course website when available. There is no assigned textbook. Copies of published research articles of interest will be distributed in class when appropriate.

Two books are recommended for supplementation (not required but recommended) of classroom material:

HODGSON, E. and SMART, R.C.:  Introduction to Biochemical Toxicology. Wiley and Sons, New York, Hardcover: 902 pages, Publisher: Wiley; 4 edition (August 18, 2008). ISBN-10: 04701021 1X, ISBN-13: 978-0470102114.

A comprehensive introductory text.

CASARETT AND DOULL’s Toxicology: The Basic Science of Poisons. 7th edition ( November 20, 2007), McGraw-Hill, New York, pp. 1280. Edited by Curtis D. Klaassen. ISBN-10: 0071470514; ISBN-13: 978-0071470513. Hardback.

An in-depth treatment of toxicology, suitable as a long-term reference for students who intend to specialize in this field.