The best protection against environmental mutagens is to identify them before they ever come into general use. But it is always possible that some substance will escape detection and affect a large number of persons without this being realized until later generations. This article considers ways in which such a genetic emergency might be promptly detected. A mutation-detecting system should be relevant in that it tests for effects that are as closely related as possible to those that are feared. It should be sensitive enough to detect a moderate increase in mutation rate, able to discover the increase promptly before more damage is done, responsive to various kinds of mutational events, and designed in such a way as to maxi mize the probability that the Gause of an increase can be found. Methods based on germinal mutation necessarily involve enormous numbers of persons and tests. On the other hand, with somatic mutations the individual cell becomes the unit of measurement rather than the in dividual person. For this reason, I think that somatic tests are preferable to germinal tests, despite the fact that it is germinal mutations which are feared.

Chemical Mutagens: Principles and Methods for Their Detection: Volume 2

Science & Math

Hollaender, Alexander

Chemistry

New York, New York, U.S.A.: Plenum Pub Corp

Volume 8 of Chemical Mutagens covers a wide range of topics in this continuously changing field. This volume includes chapters on the detection of genetic damage in mammalian sperm both at specific loci and over the entire genome. The discussion of in vitro techniques for working with mammalian cells covers not only specific locus assays but also cellular activation systems. Another chapter extensively discusses the need for a revised protocol for the micronucleus assay. Structure activity relationships are investigated in a chapter dealing with hair dye constituents. One of the most comprehensive chapters deals with problems associated with the detection of mutagenic effects in defined human populations. Finally, there is a detailed presentation of a comprehensive study tabulating the genetic bioassay data on some known or suspected human carcinogens. In keeping with our policy of publishing important legislation in the area of chemical mutagens, we have also included the Council of the European Communities Directive of 18 September 1979. Frederick J. de Serres Research Triangle Park, North Carolina vii Contents Chapter 1 Detection of Effects of Mutagens in Human Populations George R. Hoffmann 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Monitoring Progeny for Evidence of Germ-Cell Mutations. . . . . 3 2. 1. The Classical Approach: Phenotypic Monitoring . . . . . . . 3 2. 2. Monitoring for Changes in Gene Products . . . . . . . . . . . 7 3. Detection of Gene Mutations in Somatic Cells. . . . . . . . . . . . . 9 3. 1. Drug-Resistant Lymphocytes . . . . . . . . . . . . . . . . . . . . . . 9 3. 2. Hemoglobin Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 4. Nongenetic Indicators of Mutagen Exposure . . . . . . . . . . . . . 21 4. 1. Alkylation of Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 4. 2. DNA Damage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Chemical Mutagens. Principles and methods for their detection. Volume 4

Physics

Springer

Aspects of genetic engineering research emphasized in this volume are applications to plants (crop plants and grass, both important for human needs) and new methodologies, such as Tar cloning, which make it much easier to isolate specific regions from complex genomes. Another subject discussed is linear DNA replication of prokaryotes.

Genetic Engineering: Principles and Methods. Volume 3

Setlow, Jane K.

Biological Sciences

Plenum, New York and London

Like many genetic engineers, I have recently been receiving the atten tion of various venture capital companies, international drug houses and Members of Parliament. I will not discuss which of these approaches are most welcome, but it did cause me to consider the speed of advance in genetic engineering, and the implications of this rapid growth. There were few who anticipated it - only five years ago, most scientists thought applications would come at the end of the century, yet we see products such as insulin and interferon already available for clinical testing. In Europe in general and Britain in particular, this explosive growth in our own field has coincided with a general industrial depression and a marked reduction in funding for biomedical research. The brain drain from Britain is a serious matter, for we are losing the best of our younger scientists, on whom we would rely to train the next generation of molecular biologists. These volumes have come from British labs (mostly because I happen to be based in London, and my contacts and friends are here), and I feel that the quality of the con tributions also shows that our current research is of a high standard.

Genetic Engineering: Principles and Methods Volume 4

This symposium is the third in a series featuring the propaga tion of higher plants through tissue culture. The first of these symposia, entitled "A Bridge Between Research and Application," was held at the University in 1978 and was published by the Technical Information Center, Department of Energy. The second symposium, on "Emerging Technologies and Strategies," was held in 1980 and pub lished as a special issue of Environmental and Experimental Botany. One of the aims of these symposia was to examine the current state of-the-art in tissue culture technology and to relate this state of technology to practical, applied, and commercial interests. Thus, the third of this series on development and variation focused on embryogenesis in culture: how to recognize it, factors which affect embryogenesis, use of embryogenic systems, etc.; and variability from culture. A special session on woody species again emphasized somatic embryogenesis as a means of rapid propagation. This volume emphasizes tissue culture of forest trees. All of these areas, we feel, are breakthrough areas in which significant progress is expected in the next few years.

Tissue Culture in Forestry and Agriculture (Basic Life Sciences, 32)

Henke, Randolph R.

Hughes, Karen W.

Constantin, Milton J.

Wilson, Claire M.

This volume is the first of a series concerning a new tech­ nology which is revolutionizing the study of biology, perhaps as profoundly as the discovery of the gene. As pointed out in the introductory chapter, we look forward to the future impact of the technology, but cannot see where it might take us. The purpose of these volumes is to follow closely the explosion of new tech­ niques and information that is occurring as a result of the newly­ acquired ability to make particular kinds of precise cuts in DNA molecules. Thus we are particularly committed to rapid publication. Jane K. Setlow Alexander Hollaender v INTRODUCTION AND HISTORICAL BACKGROUND 1 Maxine F. Singer CLONING OF DOUBLE-STRANDED cDNA . . 15 Argiris Efstratiadis and Lydia Vi11a-Komaroff GENE ENRICHMENT . . • • . . . . . 37 M. H. Edgell, S. Weaver, Nancy Haigwood and C. A. Hutchison III 51 TRANSFORMATION OF MAMMALIAN CELLS . . . . . M. Wig1er, A. Pe11icer, R. Axel and S. Silverstein CONSTRUCTED MUTANTS OF SIMIAN VIRUS 40 73 D. Short1e, J. Pipas, Sondra Lazarowitz, D. DiMaio and D. Nathans STRUCTURE OF CLONED GENES FROM XENOPUS: A REVIEW 93 R. H. Reeder TRANSFORMATION OF YEAST 117 Christine lIgen, P. J. Farabaugh, A. Hinnen, Jean M. Walsh and G. R. Fink THE USE OF SITE-DIRECTED MUTAGENESIS IN REVERSED GENETICS 133 C. Weissmann, S. Nagata, T. Taniguchi, H. Weber and F. Meyer AGROBACTERIUM TUMOR INDUCING PLASMIDS: POTENTIAL VECTORS FOR THE GENETIC ENGINEERING OF PLANTS . 151 P. J. J. Hooykaas, R. A. Schi1peroort and A.

Genetic Engineering: Principles and Methods Volume 1

Setlow, Jane K. K.

As editor I want especially to thank Dr. Ernst Freese for helpful co operation in preparing these volumes, and to express my appreclatlOn to Drs. Kurt Hirschhorn and Marvin Legator, the other members of the editorial board. Alexander Hollaender January 1971 Preface The purpose of these volumes is to encourage the development and ap plication of testing and monitoring procedures to avert significant human exposure to mutagenic agents. The need for protection against exposure to possibly mutagenic chemicals is only now coming to be generally realized. The recently issued Report of the Secretary's Commission on Pesticides and Their Possible Effects on Health (the Mrak Report-U.S. Department of Health, Education and Welfare, December 1969) has made an important start. Its Panel on Mutagenicity recommends that all currently used pesticides be tested for mutagenicity in several recently developed and relatively simple systems. Whether recommendations such as these are actually put into effect will depend on convincing government, industry, and the public that the problem is important, that the proposed tests would be effective, and that they can be conducted at a cost that is not prohibitive. Why is it important to screen environmental agents for mutagenic activity? To those who will read this book, the answer is self-evident. The sine qua non of all that we value and all that we are is our genetic heritage.

Chemical Mutagens: Principles and Methods for Their Detection Volume 1

The ready acceptance and wide demand for copies of the first two volumes of Chemical Mutagens: Principles and Methods Jar Their Detection have demon strated the need for wider dissemination of information on this timely and urgent subject. Therefore, it was imperative that a third volume be prepared to include more detailed discussions on techniques of some of the methods that were presented from a theoretical point of view in the first two volumes, and to update this rapidly expanding field with current findings and the new developments that have taken place in the past three years. Also included is a special chapter by Dr. Charlotte Auerbach giving the historical background of the discovery of chemical mutagenesis. Methods for recognizing mutagenic compounds in vitro are a necessary preliminary step toward arriving at satisfactory solutions for recognizing significant mutation rates in man, which must be done before our test tube methods of detection can be considered reliable. Two chapters in this volume make important contributions to this problem. Due to the increasing activity in efforts to perfect techniques for detecting chemical mutagens and their effects on man, it is planned to continue this series of volumes as necessary to keep abreast of current findings.

Chemical Mutagens: Principles and Methods for Their Detection Volume 3

William C. Taylor Department of Genetics University of California Berkeley, California 94720 It is evident by now that there is a great deal of interest in exploiting the new technologies to genetically engineer new forms of plants. A purpose of this meeting is to assess the possibilities. The papers that follow are concerned with the analysis of single genes or small gene families. We will read about genes found within the nucleus, plastids, and bacteria which are responsible for agri culturally important traits. Given that these genes can be isolated by recombinant DNA techniques, there are two possible strategies for plant engineering. One involves isolating a gene from a cultivated plant, changing it in a specific way and then inserting it back into the same plant where it produces an altered gene product. An example might be changing the amino acid composition of a seed pro tein so as to make the seed a more efficient food source. A second strategy is to isolate a gene from one species and transfer it to another species where it produces a desirable feature. An example might be the transfer of a gene which encodes a more efficient pho tosynthetic enzyme from a wild relative into a cultivated species. There are three technical hurdles which must be overcome for either strategy to work. The gene of interest must be physically isolated.

Genetic Engineering of Plants: An Agricultural Perspective (Basic Life Sciences, 26)

Kosuge, Tsune

Meredith, Carole P.

This book, published by Springer since 1979, presents state-of-the-art discussions in modern genetics and genetic engineering. This focus affirms a commitment to publish important reviews of the broadest interest to geneticists and their colleagues in affiliated disciplines. Recent volumes have covered gene therapy research, genetic mapping, plant science and technology, transport protein biochemistry, and viral vectors in gene therapy, among other topics.

Genetic Engineering: Principles and Methods

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