Abraham Lincoln had thoughts about generations to come. In 1862, at the height of the Civil War, his annual message to Congress included these words: “The fiery trial through which we pass will light us down in honor or dishonor to the last generation.”
Our own fiery trial, since 9/11, counts the weapons we must expect or deploy in the near, middle and distant future. Besides more unconventional terrorist attacks, there is a futuristic panoply of guided missiles; nuclear arms; air, land and marine craft; and chemical and bioweaponry plus ionizing radiation. Just the other day, the U.S. administration allegedly lofted a trial balloon envisaging radiation directed against an enemy.
Weapons aside, ionizing radiation has been a double-edged sword since the early discoverers of radium over a century ago suffered radiation sickness and burned fingers. Today, even dental patients getting X-rays are protected by a leaden apron. But what about that patient’s children and grandchildren? Whether radiation damage can be inherited remains an open question; now a scientist in Britain hopes to give it closure. He is radiation geneticist Yuri Dubrova, at the University of Leicester.
Dubrova is senior author of a paper in the current Proceedings of the National Academy of Sciences (PNAS), released May 7, 2002, but dated May 14. Its title: “Elevated mutation rates in the germ line of first- and second-generation offspring of irradiated male mice.”
From Irradiated Grandpas To Kids, Grandkids
“The bottom line of our study its overall finding was quite surprising,” Dubrova told BioWorld Today. “What we normally expect if we directly expose animals to ionizing radiation is an increase in their mutation rate,” he continued. “Here we went further and analyzed mutation rates in the germ lines of non-exposed first- and second-generation offspring of their irradiated parent mice. And to our surprise we did find that the mutation rate in these offspring was at least three- or fourfold higher than in non-irradiated control animals.
“Many investigators have published findings showing that mutation rates in the somatic cells of irradiated male offspring are indeed elevated,” Dubrova observed. “But nobody has ever properly analyzed what would happen to the germ line. This is exactly what we did and report in PNAS.
“It’s hard to tell at the moment what implications this may have,” he went on, “because implication’ means: What can we say about humans?’ At the moment my co-authors and I have only pilot data on mice. And no one has ever done anything similar in humans. So, to be politically correct, I would not say that the result of our study can be extrapolated to humans because we don’t have any evidence in humans.
“However, having said this,” Dubrova said, “given the fact that there is not a great deal of difference between mice and humans in terms of genomic structure, DNA repair and all the rest one may speculate that the same is true for humans.
“Exposure to ionizing radiations in humans might also result in an elevated mutation rate in the germ line of their offspring. We exposed our male mice to acute and relatively high doses of radiation. This sort of exposure seldom happens to humans fortunately for us humans.”
The measure of radiation damage in Dubrova’s mice is genetic instability. He explained: “We analyzed mutation rates in the germ line of offspring of irradiated parents, and found that the rate was up. This is clear-cut evidence that the cells of these animals are genetically unstable. They manifest genetic instability in their germ-line cells and also in their somatic cells. So instead of producing a few mutant cells, they produce instead more mutated than normal ones. And this by definition is genomic instability.
“If you have it manifested in the cells of these offspring,” he pointed out, “this could potentially lead to a higher rate of cancer amongst them. This occurs because cancer is a genetic disease in a way, and you need two or three genes to be mutated for the cell to become transformed into a cancerous cell.
“We did this study because a couple of years ago we published the first-ever evidence that the offspring of irradiated CBA/H parent mice showed instability. Then we decided to ask: Would the same thing happen if we exposed other inbred strains?’ So we analyzed three strains of mice CBA/H, BALB/c and C57BL/6. In all three we found that the non-irradiated offspring of irradiated parents showed genetic instability. Then we analyzed the offspring of male mice exposed to fission neutrons a special sort of high-energy radiation but also X-rays. Both types of exposure resulted in instability in the non-irradiated offspring of irradiated males.
“And most importantly for all of us,” he announced, “we analyzed stabilities of the first- and second- generation offspring. And we went further, from sons and daughters to grandchildren of irradiated male parents. And to our surprise we found that the mutation rate in the grandchildren was also up, with the level of instability in the mutation rate itself similar to the first-generation offspring. So the whole thing persists in generations; it doesn’t go down.”
Wanted: Extended Human Affected Families
The ionizing radiation to which people are subjected is not entirely from medical diagnoses.
“Radiotherapy against cancer at high doses of radiation is normally beamed precisely to the target tissue,” Dubrova noted. “So the rest of the patient’s body is protected. The whole-body doses we applied to our mice would be very high for humans. So if a similar effect does exist in humans, then we are looking for appropriate exposure levels.”
Dubrova is contemplating conducting a survey of human populations some day, somehow. “What we need to have,” he said, “is not only parents but we need their children and their grandchildren. If the relevant population is available, I would be delighted. People involved in the short emergency work around the melted-down Chernobyl nuclear power plant were exposed to very high doses of radiation. But there were very few of those individuals. Most probably a survey could turn to some people exposed to Hiroshima and Nagasaki and perhaps some other nuclear accidents,” he concluded, “such as atomic weapons testing during the Cold War.”