Radiation Biology Research Are radiation induced effects observed in the cells of C. Elegans important in

human tissues? Darlene Jones – NPI E3 Teacher – Summer 2011

Columbia High School/Columbia-Brazoria ISD

Dr. John Ford, Associate Professor, Department of Nuclear Engineering, Texas A & M University

The practical application of nuclear physics (the study of radiation and matter)

The design, building and operation of nuclear fission systems (nuclear weapons and nuclear reactors)

Effective handling of nuclear wastes and environmental protection, nuclear fuel technology

Effective and safe use of radioactivity in the medical field (imaging and cancer therapy)

What is nuclear engineering?

Research area is interdisciplinaryHealth physicists are involved in understanding, evaluating, and controlling the potential risks to the population from radiation relative to it’s benefits

Radiological Health EngineersHealth Physics/Medical Physics

Radiological Health Engineering:

University of Tennessee Ph.D. 1992 Biomedical Sciences Dissertation Title: Effects of Alpha-Particle Radiation on Rat Tracheal Epithelial Cells.

Mississippi State University M.S. 1986 Nuclear Engineering Thesis Title: A Computer Analysis of Damage to Human Tissues by Neutrons Using Monte Carlo Techniques.

Mississippi State University B.S. 1982 Nuclear Engineering

Dr. John Ford

Graduate LevelRadiation CarcinogenesisRadiation Biology Internal Dose Techniques Worker Physiology Special Topics in Radiation Biology Health Physics Instrumentation Undergraduate LevelIntroduction to Nuclear Engineering IFoundations of Engineering INuclear Detection & Isotope Laboratory Nuclear Engineering Experiments Operational Health Physics for Advanced ReactorsSubcritical Experimentation and Modeling Undergraduate HonorsModern Techniques in Cancer ResearchApplications of Radiation to Modern ProblemsEngineering People

Some of the courses taught by Dr. Ford:

Research Area:Dr. Ford’s research deals with the response of tissues to ionizing radiation.

The cosmic radiation that astronauts are exposed to in space represents a risk during space travel.

Dr. Ford is interested in the effects of HZE particles on humans in space; therefore, he has worked with researchers at the Johnson Space Center and has had research funded by NASA and NSBRI.

HZE stands for a component of cosmic radiation consisting of energetic heavy (H) nuclei (atomic number 3 or greater); so named for their high atomic number (Z) and energy (E).

Radiation – Two Types

The C. elegans research project uses alpha particles (helium ions) to irradiate the specimens. This is a form of ionizing radiation.

The electromagnetic spectrum is electromagnetic radiation. Ionizing radiation is particle radiation. Examples of particles include hydrogen protons and helium ions.

Nuclear engineers must design systems that use radiation safely and reduce the public’s exposure to radiation.

Ongoing question:

How much ionizing radiation exposure is safe to humans?

Do cells that surround a cell exposed to ionizing radiation undergo any cellular changes attributable to the radiation exposure?

Enter the “excellent in vivo model organism for radiation biology – C. Elegans

Research Question:

This nematode lives in the soil, eats bacteria, and is about 1 mm in length.

Organism has simple growth conditions and reproduces rapidly with a life span of approximately 2-3 weeks.

The cell lineage of the organism is known and does not vary.

The organism can be easily genetically engineered for research purposes.

The genome for C. elegans has been completely sequenced.

C. Elegans - excellent ”in vivo” model for radiation biology

Anatomy & Life Cycle of C.elegans

Note: Size and simple anatomy of the animal

Dr. Ford’s research irradiates worms that are at L1 stage, then observes the worms as they mature to the adult stage. The L1 stage occurs about 4 hours after eggs hatch.

Using genetically engineered C. Elegans to allow for specific targeting of intestinal cells

The specific intestinal cells of the gut are glowing, which makes exact targeting of the micro beam precise (allowing for the irradiation of one cell).

Particle Source

Accelerator Beam line

Collimators and Irradiation Stage

Collimator-device that filters a stream of rays in order that only those rays traveling parallel to the one direction are allowed through

Electron Beam

Once the worms have grown to the L4 stage, they are fixed and treated with a DNA stain.

This stain allows the nuclei of the cells to be visible to the researcher.

*****Remember: what we are trying to see is if the cells surrounding a cell exposed to radiation also experience changes to their cellular DNA.

The following is some of the data resulting from this research:

Data and Conclusions

Quantitation of Anaphase Bridges in the Intestinal Cells of C. elegans

Irradiate Newly-Hatched L1 Larvae

or

L1 stage Dicentric Lesion:L4 binucleate

cell with bridge

Normal L4 stage: Binucleate polyploid

cell.

WT Dose response using several radiation species

Fluence (particles/cm2)

1e+5 1e+6 1e+7 1e+8 1e+9 1e+10 1e+11 1e+12

% c

ells

with

ana

phas

e br

idge

s

0

20

40

60

80

100Co-60 JANUS no 1 GeV Fe 570 MeV Ar 600 MeV Fe 670 MeV Si 215 MeV He 585 MeV Ne 155 MeV Proton

1 2 3 4 5 6 7 8 9

Worm 95

Worm 66

Worm 96

Worm 50

32 4

3 4 5

3 4 5

3 4 5 6

Examples of Anaphase Bridges in Non-targeted Cells

1 2 3 4 5 6 7 8 9

1 2 3 4 5 6 7 8 9

1 2 3 4 5 6 7 8 9

Bystander Effect was observed. Bystander effect is:An effect/change in the cells surrounding the

irradiated cell. This slide illustrates the increase in p53 (transcriptase enzyme) levels and elevated SCE levels (Sister Chromatid Exchange) in the cells that surround the irradiated cell.

These observations then raise these questions:1) Is the bystander

effect good or bad?

2) How is this signal communicated between these cells?

Future research will attempt to answer these questions.

Back to the original question…These tiny animals are assisting mankind by helping us to answer the question:

How much exposure to ionizing radiation is a risk to our health?

These exposure levels are increasing, as medical imaging and radiation therapies become more common in society, we need to know our long term risk.

Radiation biology & radiation health engineers find the answers to these questions.

Procedures in LabLocating C. elegans (Worms) in the Petri Dishes that are smaller that 1mm in length

Transfer of C. elegans (Worms) using micropipettes

C. elegans made news when it was discovered that specimens had survived the Space Shuttle Columbia disaster in February 2003.

Descendants of the worms that were aboard Columbia

in 2003 were launched into space on Endeavour for the STS-134 mission on May 16, 2011.

---Wikipedia.org

C.elegans in the news:

Upcoming Research:Studying the effects of radiation on the micro vascular tissue of the wings of pallid bats.

Will surrounding tissue areas reflect cell damage? At what dose levels?

Why and how does the cellular damage occur?

Texas A & M University – E3 Program Dr. John Ford – TAMU Nuclear EngineeringNational Science FoundationNuclear Power InstituteTexas Workforce Commission

Acknowledgments