ENVR 442 / TOXC 442 / BIOC 442
BIOCHEMICAL AND
MOLECULAR TOXICOLOGY
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Fall 2009 |
3 credit hours |
3:30-4:45, Tuesdays & Thursdays |
0003 |
PREREQUISITES
Any combination of two courses in biochemistry, molecular biology, cell
biology, or cell physiology (or permission of course director).
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Ivan Rusyn (Course director) |
0031 |
iir@unc.edu |
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Louise M. Ball |
158 Rosenau |
lmball@unc.edu |
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Phil Smith |
1317 Kerr |
pcs@email.unc.edu |
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Kim Brouwer |
3205 Kerr |
kbrouwer@unc.edu |
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David Threadgill |
NCSU |
threadgill@ncsu.edu |
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Stephen Ferguson |
CellzDirect, Inc. |
Stephen.Ferguson@lifetech.com |
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Rebecca Fry |
0032 Hooker |
rfry@unc.edu |
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Thomas O’Connell |
The Hamner |
tom_oconnell@med.unc.edu |
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Igor Pogribny |
NCTR/FDA |
IPogribny@nctr.fda.gov |
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David Dix |
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Dix.David@epamail.epa.gov |
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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
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1 |
Tuesday, August 25, 2009 |
I. Rusyn |
Overview of the science of toxicology |
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2 |
Thursday, August 27, 2009 |
L. Ball |
Metabolism of xenobiotics I (general overview); TCDDLancet; TCDDExperientiaPoiger |
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3 |
Tuesday, September 1, 2009 |
L. Ball |
Metabolism of xenobiotics II (phase 1 metabolism); GrapefruitPayneJPET; Guengerich_2008 |
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4 |
Thursday, September 3, 2009 |
P. Smith |
Metabolism of xenobiotics III (phase 2 metabolism); UGT Lecture,9.2009; Testa,Review,2008 |
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5 |
Tuesday, September 8, 2009 |
K. Brouwer |
Metabolism of xenobiotics IV (transporters); Chandra_Brouwer_2004; Klaassen_2008 |
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6 |
Thursday, September 10, 2009 |
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Induction of metabolism by toxicants; Goodwin1999; Jonesetal 2003; Wang 2003 |
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7 |
Tuesday, September 15, 2009 |
G. Pollack |
Toxicokinetics and toxicodynamics |
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8 |
Thursday, September 17, 2009 |
I. Rusyn |
Model systems and organisms in toxicology; Dambach 2005 ; Collins 2008 |
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9 |
Tuesday, September 22, 2009 |
D. Threadgill |
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Thursday, September 24, 2009 |
Examination I (in class) |
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10 |
Tuesday, September 29, 2009 |
I. Rusyn |
Biomarkers of toxicity ; Goodsaid et al 2008; NTP Biomarkers Workshop 2006 |
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11 |
Thursday, October 1, 2009 |
I. Rusyn |
Reactive oxygen species; Kensler 2007; Antioxidant enzymes and functions |
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12 |
Tuesday, October 6, 2009 |
I. Rusyn |
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13 |
Thursday, October 8, 2009 |
R. Fry |
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14 |
Tuesday, October 13, 2009 |
I. Rusyn |
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15 |
Thursday, October 15, 2009 |
I. Rusyn |
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16 |
Tuesday, October 20, 2009 |
I. Pogribny |
Role of epigenetic events in responses to toxic agents; Baccarelli_CurrOpinPediatr_2009 |
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17 |
Tuesday, October 27, 2009 |
I. Rusyn |
Chemical-induced carcinogenesis ; NTP levels of evidence; Nebert & Dalton 2006 |
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18 |
Thursday, October 29, 2009 |
I. Rusyn |
Role of genetic polymorphisms in responses to toxic agents; Walko & McLeod 2009; Frueh et al 2008 |
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Tuesday, November 3, 2009 |
Examination II (in class) |
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19 |
Thursday, November 5, 2009 |
D. Dix |
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20 |
Tuesday, November 10, 2009 |
I. Rusyn |
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21 |
Thursday, November 12, 2009 |
I. Rusyn |
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22 |
Tuesday, November 17, 2009 |
I. Rusyn |
Gene expression profiling in
toxicology; Frueh 2006; Dix et al 2006 |
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23 |
Thursday, November 19, 2009 |
I. Rusyn |
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24 |
Tuesday, November 24, 2009 |
T. O’Connel |
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25 |
Tuesday, December 1, 2009 |
D. Dix |
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26 |
Thursday, December 3, 2009 |
J. Swenberg |
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27 |
Tuesday, December 8, 2009 |
J. Swenberg |
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Tuesday, December 15, 2009 |
Examination III (in class) |
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Thursday, December 17, 2009 |
Take home Final Exam is due |
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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
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:
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At least 90% of the Maximum score ( “H-to-P cutoff”) |
H |
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At least 80% of the Median score (“P-to-L cutoff”) but less than 90% of the maximum score |
P |
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Between 70% and 79.99% of the Median score (“L-to-F cutoff”) |
L |
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Below 70% of the Median score |
F |
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,
A comprehensive introductory text.
CASARETT AND DOULL’s Toxicology: The Basic
Science of Poisons. 7th edition ( November 20, 2007),
An in-depth treatment of toxicology, suitable as a long-term reference for students who intend to specialize in this field.