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 The personality factor: How to foster the sharing of research data
06.09.2017 | ZBW – Leibniz-Informationszentrum Wirtschaft

nachricht Europe’s Demographic Future. Where the Regions Are Heading after a Decade of Crises
10.08.2017 | Berlin-Institut für Bevölkerung und Entwicklung

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: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>