Laboratory of Environmental Mutagenesis: Summary Statement

(LEM) is one of the three scientific laboratories at the National Institute of Environmental Health Sciences. In the formation of the programs for such a laboratory, it is important to set some goals and then start to ask the "how and why" questions. The societal goal for the LEM is the prevention of increased frequency of genetic disease in the human population. That goal covers the waterfront; however, the LEM cannot possibly cover all the scientific areas necessary to accomplish that goal. Independently of how large we will grow, there will be areas left out. The next questions then become, "Which parts are we going to do and how are we going to do them?" Our approaches include: (1) development of short-term testing systems for mutagenic activity , (2) development of mammalian mutation systems which can be used to predict the risk for the human population, (3) development of monitoring systems for detection of mutations in the human population, and (4) evaluation of the fitness of populations with an increased number of mutations in the gene pool. With regard to development of short-term tests for mutagenesis screening, some pollutants in the environment are neither mutagenic nor carcinogenic by themselves but can be converted by mammalian metabolism to highly reactive and genetically active metabolites. Microorganisms have only a fraction of the toxification-de-toxification mechanisms that a mammal has. To screen for mutagenicity in mammals, however, is extremely expensive and time-consuming, whereas many quantitative mutation systems exist today in microorganisms. Therefore, in the development of the short-term tests we have to combine the microbial mutation system with the drug metabolism of the higher animal. This can be done by homogeniz-ing organs of laboratory animals and preparing various enzyme fractions and testing them for their ability to form active metabolites from non-active parent compounds. But by homogenizing an organ and fractionating it into various parts, the efficiency of the activation pathways and balance between the toxification and detoxification mechanisms may be destroyed. This problem can be avoided by injecting the indicator organism into the bloodstream of the animal and treating the animal with the compound under test and later isolating the microorganism and measuring mutations in them. The microorganisms, however, are not inert components, lacking any metabolism. Since they do have their own activation and detoxification systems , it is very important to know which part of the activation is due to the microorganism …