ENVR 442 / TOXC 442 / BIOC 442

BIOCHEMICAL AND MOLECULAR TOXICOLOGY

Spring, 2007

Call No. 25464, Section 001, 3 credit hours

3:30-4:45, Tuesdays & Thursdays

0003 Hooker Research Center


Prerequisites

Faculty

Course Purpose

Course Description

Class Schedule

Grades

Reading Materials


PREREQUISITES

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


FACULTY

Ivan Rusyn (director)

0031 Hooker Research Center

iir@unc.edu

843-2596

David Holbrook

5114B Bioinf. Bldg.

david_holbrook@unc.edu

966-4685

David Threadgill

4340 MBRB

dwt@med.unc.edu

843-6472

Edward LeCluyse

CellzDirect, Inc.

edl@cellzdirect.com

545-9959

William Kaufmann

31-325 LCCC

william.kaufmann@pathology.unc.edu

966-8209

James Swenberg

2002 Hooker Research Center

james_swenberg@unc.edu

966-6139



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

Thursday, January 11, 2007

I. Rusyn

Markers of toxicity ( reading1, reading2)

   
 
 

2

Tuesday, January 16, 2007

D. Holbrook

Metabolism of xenobiotics IGuengerich, 2003Guengerich, 2004

3

Thursday, January 18, 2007

D. Holbrook

Metabolism of xenobiotics II; Shimada, 2006

   
 
 

4

Tuesday, January 23, 2007

D. Holbrook

Metabolism of xenobiotics III

5

Thursday, January 25, 2007

I. Rusyn

Reactive oxygen species I ; handouts ; reading

   
 
 

6

Tuesday, January 30, 2007

I. Rusyn

Reactive oxygen species II ; handouts ; Kwak, 2004

7

Thursday, February 1, 2007

D. Holbrook

Protective systems against toxicity I; Lu 1999; Marzullo 2005; Miles et al 2000

   
 
 

8

Tuesday, February 6, 2007

E. LeCluyse

Induction of metabolism by toxicants ( handouts )

9

Thursday, February 8, 2007

D. Holbrook

Protective systems against toxicity II; Klaassen et al 1999

   
 
 
 

Tuesday, February 13, 2007

   Examination I (in class)

10

Thursday, February 15, 2007

I. Rusyn

Role of genetic polymorphisms in responses to toxic agents         (handouts )
   
 
 

11

Tuesday, February 20, 2007

I. Rusyn

Model systems and organisms in toxicology ; handouts ;           Dambach et al 2005

12

Thursday, February 22, 2007

I. Rusyn

Mechanisms of cell proliferation ( handouts )

   
 
 

13

Tuesday, February 27, 2007

D. Threadgill

Rodent models in toxicology ; handouts; Rogner 2003

14

Thursday, March 1, 2007

R. Mailman

Toxicant-receptor interactions

   
 
 
15

Tuesday, March 6, 2007

I. Rusyn
Mechanisms of cell death ( handouts )

16

Thursday, March 8, 2007

I. Rusyn

Chemical-induced carcinogenesis; handouts; Anisimov2005;    Nebert & Dalton 2006; NTP levels of evidence

       
 

Tuesday, March 13, 2007

  No class - Spring Break

 

Thursday, March 15, 2007

       

17

Tuesday, March 20, 2007

W. Kaufmann

DNA damage and repair ( handouts )

 

Thursday, March 22, 2007

   Examination II (in class)

     

 

 

Tuesday, March 27, 2007

  Society of Toxicology Annual Meeting, Charlotte, NC

 

Thursday, March 29, 2007

       
18 Tuesday, April 3, 2007
I. Rusyn
Toxic effects of inorganic salts

19

Thursday, April 5, 2007

I. Rusyn

Toxic effects of pesticides  ( handouts )

   
 
 

20

Tuesday, April 10, 2007

I. Rusyn

Toxic effects of hydrocarbons and alcohols ( handouts )

21

Thursday, April 12, 2007

I. Rusyn

Gene expression profiling in toxicology ( handouts )                    Dix et al 2006; Frueh 2006 (required readings)

   
 
 

22

Tuesday, April 17, 2007

I. Rusyn

Proteomics applications in toxicology ( handouts )                      Fountoulakis and Sutter 2002; Heijne et al 2003

23

Thursday, April 19, 2007

I. Rusyn

Metabolomics applications in toxicology ( handouts )                  Thomas and Ganji 2006

   
 
 

24

Tuesday, April 24, 2007

J. Swenberg

Molecular dosimetry I ( handouts )

25

Thursday, April 26, 2007

J. Swenberg

Molecular dosimetry II

       
 

Tuesday, May 1, 2007

   Examination III (in class)

     
 

Tuesday, May 8, 2007

   Final Examination (open book) due by 10 am

   Guidelines for exam

   Reading 1

   Reading 2

   Reading 3

   Reading 4



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:  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 25
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 total course  grade. 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 January/February 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 total course grade.

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 total course grade.

Total Points Scored

(%)

Descriptor

Final Grade

300 - 270

(100 - 90)

Excellent

H

269 - 255

(90 - 85)

Very Good

P+

254 - 225

(85 -75)

Good

P

224 - 210

(75 - 70)

Mostly Satisfactory

P-

209 - 180

(70 - 60)

Marginally Adequate

L

Less than 180

(<60)

Insufficient

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 of classroom material:

HODGSON, E. and SMART, R.C.: Introduction to Biochemical Toxicology. Wiley and Sons, New York, 2001, Third Edition, pp. 721. ISBN 0-471-33334-4, Hardback.
A comprehensive introductory text.

CASARETT AND DOULL's Toxicology: The Basic Science of Poisons. Sixth Edition, McGraw-Hill, New York, 2001, pp. 1111. Edited by Curtis D. Klaassen. ISBN 0-07-134721-6, Hardback.
An in-depth treatment of toxicology, suitable as a long-term reference for students who intend to specialize in this field.