Ever since the atomic bombs dropped on Japan created the world's largest experiment on the effects of radiation on humans, people have puzzled over not only just what these effects could be, but also if they could be passed on to the children of those exposed. In the past, researchers have shown in mice that some effects -- in the form of genetic mutations -- can indeed be passed to offspring and cause health effects.
Now Lynn Wiley and her colleagues at the University of California, Davis, and Lawrence Livermore National Laboratory have used a very sensitive model they developed to demonstrate that if a male mouse is exposed to radiation, he may pass on detrimental effects not only to his children, but also to his grandchildren, and even great-grandchildren.
Wiley will present her work at a conference Nov. 8-9 in Japan called "Bioregulation of Radiation Response: Genetic Instability." Most of the information she presented was published this summer in the journals Radiation Research and Mutation Research.
Wiley says that her "environmentally relevant" assay -- using amounts of radiation that compares to what a person might receive during radiation therapy for cancer -- confirms what the Japanese have been saying for years; that the effects of radiation can be passed down through generations. Her results are controversial but she says, "so far, no one's been able to knock it down ... Every molecule of that paper has been turned over, and it hasn't been shot down."
"There is a big difference between transmission, which means passing on effects to the children, and heritability, which means passing it on to all future generations," said Wiley, a professor of medicine with the campus Institute of Toxicology and Environmental Health. "Heritability means that it has survived a complete round of DNA replication, and that it is stable in the DNA of the sperm."
The method that Wiley and her colleagues used is much more sensitive than those used in conventional mouse studies, which use hundreds of thousands of mice. Hers uses only about 75 mice at a time. According to Wiley, what is new about her findings is that she saw the radiation effects in the small numbers of mice she used, indicating that the radiation is affecting DNA non-specifically; in other words, it's affecting many genes.
Wiley exposed eight or so male mice at a time to the radioisotope Cesium-137, and allowed these mice to mate with females once a week for eight weeks, to cover the sperm-making history of the father. The sons of these irradiated fathers were allowed to mate with females beginning at eight weeks of age to produce the grandchildren that were used in Wiley's study.
In the assay developed by Wiley more than 10 years ago, embryos consisting of only four cells are removed from the mother. These cells are then combined with four cells from another embryo -- one without a history of radiation -- and allowed to multiply several times. Then the scientists count the total number of cells (one of the embryos has a special marker so it can be distinguished from the other). If there are fewer cells from the cells that received radiation, then they have a growth disadvantage from inherited DNA damage, according to Wiley.
Wiley said she found a significant reduction in cell reproduction and growth in the offspring of mice that had been irradiated six or seven weeks before conception, corresponding to a sensitive stage in sperm development. These grandchildren mice also weigh less than normal mice and their sperm are less efficient at fertilization.
Wiley suspects her fairly simple, yet exquisitely sensitive, cellular assay could be used to predict inherited effects of radiation in future generations of animals. The reproductive toxicology professor is now continuing her studies to look at lower doses of radiation, and to determine on a genetic level what the changes are that are induced by radiation.
"The human side of these studies is that we already have in mice documented irradiation effects that are passed on to future generations, ones that are causing cell growth and reproduction changes," she said. "If you mess around with that, you can't help but wonder if these changes will turn out to be cancerous or impair reproduction."
Wiley's work was funded by the National Institutes of Health.