A chemical used for years in genetic experiments has been found to be far more likely than radiation to cause mutations in mammals according to biologists at the Oak Ridge National Laboratories in Tennessee.
The chemical, called ethylnitrosourea or ENU, is not found in nature nor is it used anywhere except in laboratories by scientists studying genetic change, said Dr. William L. Russell, an internationally known geneticist who works at Oak Ridge. ENU, used previously to induce mutations in food grains and in fruit flies, has been found to produce five times as many mutations in mice as does a radiation dose of 600 roentgen.
The Oak Ridge researchers are the first to identify a chemical cause for mutations in mammals, said Russell, who added the findings raise questions about a wide range of chemicals and their effect on humans. "We think it quite likely that other compounds to which [ENU] is related might also be mutagenic," or mutation-causing, Russell said.
ENU is related chemically to nitrosamines, known cancer-causing agents produced when preserved meat is cooked; they also are found in beer. The one nitrosamine tested so far did not produce mutations, Russell said, but he said many more experiments to assess the mutagenic effect of nitrosamines were needed. ENU is also similar to the so-called alkyl group of chemicals, those with the terms methyl, ethyl, propyl and butyl in their names. Methyl and ethyl alcohols, the common wood and drinking alcohols, have been tested and found free of mutagenic effects, Russell said.
Laboratory mice were given "a very small dose" of ENU -- one thousandth of a teaspoon, Russell said.
Seven "marker" genes in the first-generation offspring were then checked for evidence of change in the color and markings of the mice and in the structure of their ears. The mutation rate was five times that produced by 600 roentgen of radiation, a dose that would be fatal to humans, and 87 times the normal rate of mutation in mice.
It was also 15 times greater than the mutation rate from another chemical called procarbazine, previously the most genetically hazardous substance known.
"We know that if we get mutations in the marker genes that there are many, many more that we're not scoring," Russell said. "There are probably dozens or hundreds more that would show up during crossbreeding."
The research sample of ENU was produced by the Bio-Clinical Laboratories of Bohemia, N.Y., one of several makers of the simple hydrocarbon-based compound, Russell said. Its use in research labs poses only a minor threat to laboratory workers, although precautions are necessary in its handling, he added.
The National Academy of Sciences this week published the findings of Russell's research team. "There is a lot of specualtion about what exactly this chemical does to the DNA," the human chemical agent that makes up genes and chromosomes, Russell said. "Other compounds simply don't do it."
The findings, he said, should increase public concern about possible dangers of chemicals in the environment, especially when compared to the risks of radiation. "This indicates that the mammalian body does not have the defense mechanisms against some chemicals that we thought it had against all of [the mutagens]," he said.