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Research / Discovery

Small fish helps answer big questions

February 18, 2009

The damaging effects of radiation on the DNA of cells are well documented. What is less understood is why the cells of some individuals are more sensitive to radiation exposure while cells of others are more resistant to those effects, or how low doses of radiation over longer periods of time affect DNA damage and repair.

A very small Japanese fish is helping researchers at Colorado State University to answer these very big questions, along with other mysteries of radiation exposure and DNA damage and repair.

Small ricefish found in SE Asia

The medaka is a small ricefish found in the rice paddies of Southeast Asia and is popular in aquariums (a school of medaka also traveled into space in 1994 aboard the space shuttle Columbia).

The medaka, Oryzias latipes, is a common model organism used in biological research because it is simple, tolerant of temperature changes, shortlived, reproductively prolific, hardy, and easy to rear in the laboratory. It can withstand cold and can be shipped easily, important to the research work in John Zimbrick’s (pictured below) laboratory because his fish routinely have to make the trek from Georgia to Colorado. Working with the medaka fish has the added benefit of using a low-cost model system to conduct experiments that would be costprohibitive with a mammalian model.

Lab studies genetic effects of low doses of radiation

“In our laboratory, we are using our fish to study the genetic effects of low doses of radiation, doses that would be similar to the doses radiation workers could be allowed to get over several years,” said Zimbrick, a professor in the Department of Environmental and Radiological Health Sciences.

“In addition, we are searching for so-called transgenerational effects in the form of mutations occurring in the offspring as a result of the exposures to the parents. For many years, the Department of Energy funded research into high-dose effects of radiation, but not too much attention was paid to low-dose effects. Legal limits for the doses workers could be exposed to were established at levels that will not produce detectable harmful effects, but few the studies have been done that show what the genetic effects of those doses might be over longer periods of time covering one or more generations of offspring.”

Zimbrick is working in collaboration with the University of Georgia’s Savannah River Ecology Laboratory, or SREL, where the medaka are exposed to set levels of radiation.

Transgenerational studies  

Following exposure, the fish are shipped to CSU where researchers are conducting transgenerational studies, looking for DNA damage, changes in gene activity and mutations in first through sixth generations of the medaka. To date, they have data for the first three generations, and samples for the fourth and fifth.

“A major early finding is that if we irradiate parents and then examine the first, second and third generations, we see an increase in special mutations called micro-satellite DNA mutations in the offspring, which we can detect if there is a change in even one of the DNA bases,” said Zimbrick.

Zimbrick said it is possible that chronic radiation exposure of parents could result in still higher mutation rates in even sixth and seventh generations, but the biological effects from these would have to be of such nature that the future generations survive in spite of the mutations. Over time these offspring may adapt to the radiation-induced mutations, becoming more genetically diverse and more resistant to radiation effects.

Fish's genetic make-up highly varied and diverse like human population

“The medaka fish is an excellent model for this type of work in that it is outbred, meaning that its genetic make-up is highly varied and diverse because it has intermingled and bred over many generations, similar to our global human population,” said Zimbrick.

The researchers will also select specimens from the lower and upper ends of the sensitivity scale, breed them, profile the genes, and look for patterns of gene activities associated with the genes involved in DNA repair. If they are successful and able to find a set of repair genes whose activities relate to individual radiosensitivity, those candidate genes may be elevated for additional study in a more complex model.

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Original story published in the College of Veterinary Medicine and Biomedical Sciences Insight magazine on pages 28-29, Fall 2008.