Study Shows Hereditary Legacy Of Radiation Exposure

Now Lynn Wiley and her colleagues at the University ofCalifornia, Davis, and Lawrence Livermore National Laboratoryhave used a very sensitive model they developed todemonstrate that if a male mouse is exposed to radiation, hemay pass on detrimental effects not only to his children, butalso to his grandchildren, and even great-grandchildren.

Wiley will present her work at a conference Nov. 8-9 in Japancalled "Bioregulation of Radiation Response: GeneticInstability." Most of the information she presented waspublished this summer in the journals Radiation Research andMutation Research.

Wiley says that her "environmentally relevant" assay -- usingamounts of radiation that compares to what a person mightreceive during radiation therapy for cancer -- confirms whatthe Japanese have been saying for years; that the effects ofradiation can be passed down through generations. Her resultsare controversial but she says, "so far, no one's been ableto knock it down ... Every molecule of that paper has beenturned over, and it hasn't been shot down.

"There is a big difference between transmission, which meanspassing on effects to the children, and heritability, whichmeans passing it on to all future generations," said Wiley, aprofessor of medicine with the campus Institute of Toxicologyand Environmental Health. "Heritability means that it hassurvived a complete round of DNA replication, and that it isstable in the DNA of the sperm."

The method that Wiley and her colleagues used is much moresensitive than those used in conventional mouse studies,which use hundreds of thousands of mice. Hers uses only about75 mice at a time. According to Wiley, what is new about herfindings is that she saw the radiation effects in the smallnumbers of mice she used, indicating that the radiation isaffecting DNA non-specifically; in other words, it'saffecting many genes.

Wiley exposed eight or so male mice at a time to theradioisotope Cesium-137, and allowed these mice to mate withfemales once a week for eight weeks, to cover the sperm-making history of the father. The sons of these irradiatedfathers were allowed to mate with females beginning at eightweeks of age to produce the grandchildren that were used inWiley's study.

In the assay developed by Wiley more than 10 years ago,embryos consisting of only four cells are removed from themother. These cells are then combined with four cells fromanother embryo -- one without a history of radiation -- andallowed to multiply several times. Then the scientists countthe total number of cells (one of the embryos has a specialmarker so it can be distinguished from the other). If thereare fewer cells from the cells that received radiation, thenthey have a growth disadvantage from inherited DNA damage,according to Wiley.

Wiley said she found a significant reduction in cellreproduction and growth in the offspring of mice that hadbeen irradiated six or seven weeks before conception,corresponding to a sensitive stage in sperm development.These grandchildren mice also weigh less than normal mice andtheir sperm are less efficient at fertilization.

Wiley suspects her fairly simple, yet exquisitely sensitive,cellular assay could be used to predict inherited effects ofradiation in future generations of animals. The reproductivetoxicology professor is now continuing her studies to look atlower doses of radiation, and to determine on a genetic levelwhat the changes are that are induced by radiation.

"The human side of these studies is that we already have inmice documented irradiation effects that are passed on tofuture generations, ones that are causing cell growth andreproduction changes," she said. "If you mess around withthat, you can't help but wonder if these changes will turnout to be cancerous or impair reproduction."

Wiley's work was funded by the National Institutes of Health.