Last updated: January 13, 2010

Spring 2010

School of Health Sciences

HSCI 540 Radiation Biology January 11 (semester begins), May 2 (class ends), May 8 (semester ends) T Th 9:00 to 10:15 a.m. in CIVL 2102 https://courses.pnhs.purdue.edu/hsci540/

Course Instructors Robert D. Stewart, Ph.D. ([email protected]) Associate Professor and Assistant Head of Health Sciences Director, Radiological Health Sciences Program http://rh.healthsciences.purdue.edu/faculty/rds.html Office Hours: Tuesday from 1:30 to 4:30 pm (in CIVL 1173B) Jeannie Poulson, D.V.M., Ph. D. ([email protected]) Associate Professor, Veterinary Clinical Sciences Director, Radiation Oncology Program, http://www.vet.purdue.edu/vcs/faculty/poulsonj.html Office Hours: by appointment (494-0346) in Lynn G578 (Veterinary Teaching Hospital)

Teaching Assistants •

Victor Yu, Ph.D. Student in Medical Physics ([email protected]). Office located in physics 096 (PHYS 96) – W from 1-3 pm and F from 2 to 4:45 pm.

Course Description This three credit hour course provides an introduction to principles and concepts underlying the biological effects of ionizing radiation at the molecular, cellular and whole-tissue level. Topics covered include selected aspects of microdosimetry, radiation damage to DNA, DNA repair mechanisms, cell-cycle kinetics (repopulation effects), cell death mechanisms and clonogenic survival, Linear Energy Transfer (LET) effects and relative biological effectiveness (RBE), oxygen effects, apoptosis, acute effects of whole body irradiation, radiation carcinogenesis, hereditary effects of radiation, the tumor control probability (TCP), clinical responses of normal tissues to radiation, cancer biology, and biological indicators of treatment effectiveness, such as biologically equivalent dose (BED) and equivalent uniform dose (EUD) concepts. Examples and discussion related to radiation therapy treatment planning and radiation protection are covered. The course emphasizes critical thinking and problem solving skills over rote memorization. Prerequisites: HSCI 312, BIOL 110 and 111 (or BIOL 415). Authorized equivalent courses or consent of instructor may be used in satisfying course pre- and co-requisites.

Website(s) • •

https://courses.pnhs.purdue.edu/hsci540/ (password required) http://rh.healthsciences.purdue.edu/fus/

Textbook •

Radiobiology for the Radiologist, 6th ed., by Eric J. Hall and Amato J. Giaccia, Philadelphia, Lippincott, Williams and Wilkins (2006).

Other Related Textbooks and Reading: •

A.H.W. Nias, An Introduction to Radiobiology, Second Edition, John Wiley and Sons, 1998 (reprinted in 2000). 1

Last updated: January 13, 2010

• • •

Spring 2010

B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, Molecular Biology of the Cell, 4th Edition, Garland Science, a member of the Taylor & Francis Group, New York, NY 2002. Optional. David Wigg, Applied Radiobiology and Bioeffect Planning. Medical Physics Publishing Corporation (July 1, 2001). Selected readings from the literature.

Course Outline This course covers most of the material recommended by the American Association of Physicists in Medicine (AAPM) in Report 77 Academic Program Recommendations for Graduate Degrees in Medical Physics (2002) as well as selected topics needed by Health Physicists to better understand the biological basis for radiation protection guidelines. The course covers all or selected portions of the material presented in • Chapter 1 Physics and Chemistry of Radiation Absorption • Chapter 2 DNA Strand Breaks and Chromosomal Aberrations • Chapter 3 Cell Survival Curves • Chapter 4 Radiosensitivity and Cell Age in the Mitotic Cycle • Chapter 5 Repair of Radiation Damage and the Dose-Rate Effect • Chapter 6 Oxygen Effect and Reoxygenation • Chapter 7 Linear Energy Transfer and Relative Biologic Effectiveness • Chapter 8 Acute Effects of Total-Body Irradiation • Chapter 10 Radiation Carcinogenesis • Chapter 11 Hereditary Effects of Radiation • Chapter 12 Effects of Radiation on the Embryo and Fetus • Chapter 14 Doses and Risks in Diagnostic Radiology, Interventional Radiology and Cardiology and Nuclear Medicine • Chapter 15 Radiation Protection • Chapter 17 Cancer Biology • Chapter 19 Clinical Response of Normal Tissues • Chapter 20 Model Tumor System • Chapter 21 Cell, Tissue, and Tumor Kinetics • Chapter 22 Time, dose, and fractionation in Radiotherapy

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Last updated: January 13, 2010

Spring 2010

Course Objectives Upon completion of this course, students should: • • • • •

Understand the spatial scales and time-sequence of the important physical, chemical and biological events and processes underlying the formation of lethal and non-lethal genetic damage, cell death, and cancer. Understand basic mechanisms of radiation-induced biological responses, including DNA damage and repair, cell cycle arrest, apoptosis and clonogenic survival, neoplastic transformation and cancer. Understand how selected physical (e.g., oxygen and particle linear energy transfer) and biological processes (e.g., repair and cell division) modify molecular and cellular responses to ionizing radiation and influence the collective response of cancerous and normal tissue. Understand and be able to design biologically equivalent fractionation schedules for externalbeam radiation therapy and brachytherapy. Understand and be able to quantify tissue and cellular responses to low and high doses of ionizing radiation.

Students are responsible for, and may be quizzed on, all material covered in the lectures as well as material from the textbook. The lectures are designed to supplement, and not replace, the materials covered in the textbook. A list of additional textbooks, reports and journal articles related to the radiological sciences can be found in the “Related textbooks and other reading” document available on the course website.

Course Schedule and Workload Class meets in Civil Engineering Building 2117 on T and Th from 9:00 to 10:15 a.m. January 11 to April 30. Grades will be based on scores on 6 homework assignments and 14 short (10-15 minutes). Homework assignment 6 is in lieu of a final exam. Quizzes will cover material from the textbook and from the lecture notes. Announced and unannounced extra credit quizzes or assignments may be periodically offered during class throughout the semester. Makeup quizzes will only be allowed when the reason for the absence is substantial and documented. Valid examples are: illness when documented by a note from a physician and documented attendance at a funeral. Students should expect to spend approximately 4-6 hour per week outside of class reading the textbook, completing the homework assignments and studying for quizzes. Grade information will be posted on the course website (https://courses.pnhs.purdue.edu/hsci540/). A valid user account and password are required to access grade information. The username and password used to login to the site are the same ones used to login to your Purdue Career Account.

Grading Philosophy: As of the first day of class, everyone has an A. All students that demonstrate mastery of the concepts and topics covered in this course will receive an A in the course, i.e., final grades will not be assigned so that only a fixed number (%) of students receive an A or B or C. To demonstrate mastery of the material, students are required to complete a series of inter-related homework, reading assignments and quizzes.

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Last updated: January 13, 2010

Spring 2010

Specifics: The quizzes will account for 50% of the course grade (about 3.6% per quiz) and the homework assignments will account for the other 50% (about 8.3% per assignment). Additional quizzes or assignments may be given on occasion for extra credit. Letter grades will be assigned as indicated in the Table. Overall Score (%)

Quiz and Homework Assignment Due Dates (tentative) • Homework 1 (Friday January 29), Homework 2 (Wednesday February 23), Homework 3 (Friday March 12), Homework 4 (Wednesday April 7), Homework 5 (Friday April 23), Homework 6 in lieu of final exam (Tuesday May 4) • Quiz 1 (Tuesday January 19), Quiz 2 (Tuesday January 26), Quiz 3 (Tuesday February 2), Quiz 4, (Tuesday February 9), Quiz 5 (Tuesday February 16), Quiz 6 (Tuesday February 23), Quiz 7 (Tuesday March 2), Quiz 8 (Tuesday March 9), Quiz 9 (Tuesday March 23), Quiz 10 (Tuesday March 30), Quiz 11 (Tuesday April 6), Quiz 12 (Tuesday April 13), Quiz 13 (Tuesday April 22), Quiz 14 (Tuesday April 29)

Grade

min

max

Scholastic Index

A+

95.00

100.00

4.00

A

92.50

95.00

4.00

A-

88.50

92.50

3.70

B+

85.00

88.50

3.30

B

81.00

85.00

3.00

B-

77.00

81.00

2.70

C+

73.00

77.00

2.30

C

69.00

73.00

2.00

C-

65.00

69.00

1.70

D+

61.00

65.00

1.30

D

57.00

61.00

1.00

D-

53.00

57.00

0.70

F

-

53.00

-

Cheating Policy The instructor expects that no student will cheat on quizzes. Although the homework assignments are not a group project and must be individually completed, students are encouraged to discuss problem solving strategies and compare answers with classmates. However, copying a classmate’s solution or answer is considered cheating. In the unfortunate event that cheating occurs, the grade for the exam/quiz in question will be assigned an F (0%) and the cheating incident will be reported to the Dean of Students.

Attendance Policy Attendance is STRONGLY encouraged but not required. Although the topics covered in the textbook and course lectures will have considerable overlap, some materials covered in the lecture are not covered in the textbook and vice versa. Students will be responsible for, and may be tested on, materials from the textbook and the lectures. Skipping lectures and/or not reading the textbook will have a negative impact on your final grade.

Campus Emergencies In the event of a major campus emergency, course requirements, deadlines and grading percentages are subject to changes that may be necessitated by a revised semester calendar or other circumstances. Students will be notified by email in the event of a change to the course. Information about changes to the course will also be posted at https://courses.pnhs.purdue.edu/hsci540/

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Last updated: December 23, 2009

Spring 2010

HSCI 540 Radiation Biology – Course Schedule (Spring 2010) Quizzes will be held in class on days with an asterisk (*) next to them. Lecture, quiz and assignment dates may be adjusted at the discretion of the instructor. Revised due dates will be announced in class, and a revised version of the schedule will be posted on the course website (JP = Jeannie Poulson; KS = Keith Stantz; RS = Robert Stewart) Class  

Date 

Day 

Lecture Topic 

Instructor 

1 

Jan 12 

Tue 

Course Introduction and Overview (Chapter 1) 

RS 

2 

Jan 14 

Thu 

Review of Radiation Physics and Dosimetry Concepts 

RS 

3 

Jan 19 

Tue* 

Microdosimetry 

RS 

4 

Jan 21 

Thu 

Target‐Hit Theory and Bystander Effects (microdosimetry applications) 

RS 

5 

Jan 26 

Tue* 

Mechanisms of DNA damage Induction (Chapter 2, Parts of 6 and 7) 

RS 

6 

Jan 28 

Thu 

RBE for damage induction (x‐rays, protons, heavy ions, …) 

RS 

7 

Feb 2 

Tue*   Mechanisms and effects of oxygen on damage induction and complexity 

RS 

8 

Feb 4 

Thu 

BER of individual and clustered DNA lesions 

RS 

9 

Feb 9 

Tue* 

DSB repair mechanisms (HR and NHEJ) 

RS 

10 

Feb 11 

Thu 

Chromosomal Aberrations I and the linear‐quadratic (LQ) model 

RS 

11 

Feb 16 

Tue* 

Chromosomal Aberrations II (protraction factor and dose rate effects) 

RS 

12 

Feb 18 

Thu 

Hereditary Effects (Chapter 11) 

RS 

13 

Feb 23 

Tue* 

Cell Death, Neoplastic Transformation and Cancer (classic paradigm) 

RS 

14 

Feb 25 

Thu 

Risk Assessment I (LNT, DDREF, qualify factor and EUD) 

RS 

15 

Mar 2 

Tue* 

Risk Assessment II (workplace, diagnostic procedures and therapy) 

RS 

16 

Mar 4 

Thu 

Cancer Biology I (Chapter 17) 

RS 

17 

Mar 9 

Tue* 

Cancer Biology II (Chapter 17) 

RS 

18 

Mar 11 

Thu 

Effects of Radiation on the Embryo and Fetus (Chapter 12) 

JP 

‐ 

Mar 16 

Tue 

Spring Break (no class) 

  

‐ 

Mar 18 

Thu 

Spring Break (no class) 

  

19 

Mar 23 

Tue* 

Clonogenic Survival (Chapter 3); Tumor Control Probability (TCP) 

RS 

20 

Mar 25 

Thu 

Re‐oxygenation effect (Chapter 6), Cell Cycle Effects (Chapter 4) 

RS 

21 

Mar 30 

Tue* 

Isoeffect Calculations I (fractionation, oxygen and RBE effects) 

RS 

22 

Apr 1 

Thu 

Anatomic/functional imaging in therapy (target definition, GTV, PTV, CTV) 

KS 

23  24 

Apr 6  Apr 8 

Tue*  Thu 

Model tumor system (Chapter 20)  Cell, tissue, and tumor kinetics (Chapter 21) 

JP  JP 

25 

Apr 13 

Tue*   Isoeffect calculations II (Brachytherapy and repopulation effects) 

RS 

26 

Apr 15 

Thu 

Isoeffect calculations III (DVH and EUD concepts) 

RS 

27 

Apr 20 

Tue 

Dose‐Response Relationships for Model Normal Tissues (Chapter 18) 

JP 

28 

Apr 22 

Thu* 

Clinical Response of Normal Tissues (Chapter 19) 

JP 

29 

Apr 27 

Tue 

Tolerance Dose, EUD and Normal Tissue Complication Probability (NTCP) 

RS 

30 

Apr 29 

Thu* 

Biologically Guided Radiation Therapy (BGRT) 

RS 

 

May 1 

Sat 

Semester Ends 

 

Homework 6 in lieu of final exam (due on Tuesday May 4) 

 

Grades due in registrar’s office 

 

finals   

May 3‐8    May 11 

Tues