Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Jefferson Scientists Use Zebrafish Model to Show Effects of Ionizing, UV Radiation Differ During Development

31.03.2004


The results and use of the model may have implications for cancer therapy



Zebrafish may prove to be an invaluable animal model with which to screen the effects of radiation, Jefferson Medical College researchers have found.

Adam Dicker, M.D., Ph.D., associate professor of radiation oncology at Jefferson Medical College of Thomas Jefferson University and Jefferson’s Kimmel Cancer Center in Philadelphia, Mary Frances McAleer, M.D., Ph.D., a resident in the Department of Radiation Oncology at Jefferson Medical College and their co-workers compared the effects on zebrafish embryos of two types of radiation – ionizing radiation, which is the kind given to patients for cancer treatment, and ultraviolet (UV) radiation, which comes naturally from the sun.


The researchers exposed the embryos at different time points in development to different doses of ionizing and UV radiation, comparing the sensitivity of the embryos.

“We found that the zebrafish were very sensitive to the mid-blastula transition, the point in development in which the embryo goes from relying on the maternal mRNA in the yolk sac to the embryo itself controlling development,” Dr. McAleer says.

Prior to this transition, the fish are extremely sensitive to ionizing radiation, she says. But when exposed to UV light, the younger embryos were unaffected. But later, after the transition period, the embryos show morphologic damage in their development when exposed to UV radiation.

Dr. McAleer presents the team’s findings March 30 at the annual meeting of the American Association for Cancer Research in Orlando.

“We saw something unique,” she says. “We hypothesize that this may be due to the gene expression of the embryos.” The researchers say that prior to the mid-blastula transition, cells are going through the cell growth cycle without regulation, rapidly dividing. At that point, the cell cycle becomes asynchronous, with certain cells dividing at the same time – which is when differentiation and “the crux of development” occurs.

They found that much of the damage from ionizing radiation is due to breaks in both strands of the cell’s double-stranded DNA. When the fish were exposed to UV light, the DNA formed “crosslinks” in which two thymine bases form on the same strand next to each other. The cell uses entirely different repair mechanisms to fix both types of damage.

The Jefferson team performed a microarray analysis to confirm their findings. They looked at normal embryos unexposed to radiation at different time points in their development, examining different groups of genes in normal embryos involved in various types of DNA repair, including base-excision repair, mismatch repair and double-strand break repair.

They found that prior to the mid-blastula transition, the enzymes required for mismatch and base repair are elevated. “Conversely, the double-strand break repair genes aren’t expressed until following that time point,” Dr. McAleer says. “This supported our observation that this is gene expression-based. The damage we saw early in the fish exposed to ionizing radiation is related to the absence of the double-strand break repair enzymes. There is a low level of repair genes in the later fish, which is when we see UV exposure sensitivity.”

In earlier work, Dr. Dicker used zebrafish to show that while radiation and some chemotherapeutic agents damage DNA, there were different time periods in development in which the zebrafish were sensitive to either radiation or the drugs.

“In general, drugs targeted for specific enzymes are used in combination with chemotherapy agents,” he says. “We can use the zebrafish system to help us understand the mechanisms of how chemotherapy drugs work before we start adding them on.”

According to Dr. McAleer, the zebrafish as a vertebrate model with which to study cancer has several advantages. The embryos are optically transparent, meaning researchers can watch organs develop. The fish are easy to manipulate and manage, and develop into adults in a short time. Most importantly, their DNA or genome is very similar to humans.

Next, the researchers plan to use zebrafish to help them test the effectiveness of various drugs in blunting the effects of radiation.

Steven Benowitz | TJUH
Further information:
http://www.jeffersonhospital.org/news/e3front.dll?durki=17620

More articles from Studies and Analyses:

nachricht Drought hits rivers first and more strongly than agriculture
06.09.2018 | Max-Planck-Institut für Biogeochemie

nachricht Landslides triggered by human activity on the rise
23.08.2018 | European Geosciences Union

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Storage & Transport of highly volatile Gases made safer & cheaper by the use of “Kinetic Trapping"

Augsburg chemists present a new technology for compressing, storing and transporting highly volatile gases in porous frameworks/New prospects for gas-powered vehicles

Storage of highly volatile gases has always been a major technological challenge, not least for use in the automotive sector, for, for example, methane or...

Im Focus: Disrupting crystalline order to restore superfluidity

When we put water in a freezer, water molecules crystallize and form ice. This change from one phase of matter to another is called a phase transition. While this transition, and countless others that occur in nature, typically takes place at the same fixed conditions, such as the freezing point, one can ask how it can be influenced in a controlled way.

We are all familiar with such control of the freezing transition, as it is an essential ingredient in the art of making a sorbet or a slushy. To make a cold...

Im Focus: Micro energy harvesters for the Internet of Things

Fraunhofer IWS Dresden scientists print electronic layers with polymer ink

Thin organic layers provide machines and equipment with new functions. They enable, for example, tiny energy recuperators. In future, these will be installed...

Im Focus: Dynamik einzelner Proteine

Neue Messmethode erlaubt es Forschenden, die Bewegung von Molekülen lange und genau zu verfolgen

Das Zusammenspiel aus Struktur und Dynamik bestimmt die Funktion von Proteinen, den molekularen Werkzeugen der Zelle. Durch Fortschritte in der...

Im Focus: Dynamics of individual proteins

New measurement method allows researchers to precisely follow the movement of individual molecules over long periods of time

The function of proteins – the molecular tools of the cell – is governed by the interplay of their structure and dynamics. Advances in electron microscopy have...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Berlin5GWeek: Private industrial networks and temporary 5G connectivity islands

16.10.2018 | Event News

5th International Conference on Cellular Materials (CellMAT), Scientific Programme online

02.10.2018 | Event News

Major Project: The New Silk Road

01.10.2018 | Event News

 
Latest News

Unravelling the genetics of fungal fratricide

16.10.2018 | Life Sciences

Blue phosphorus -- mapped and measured for the first time

16.10.2018 | Physics and Astronomy

Berlin5GWeek: Private industrial networks and temporary 5G connectivity islands

16.10.2018 | Event News

VideoLinks
Science & Research
Overview of more VideoLinks >>>