[en] This book consists of 39 chapters. Some of the titles are: Bacillus subtilis repair test, Induced reversion using human adenovirus, The fluctuation test in bacteria, Chemical mutagenesis with diploid human fibroblasts, The specific locus test in the mouse, The bone marrow micronucleus test, and Sperm morphology in testing in mice

[en] No germinal mutagen has been documented in man, with the possible exception of radiation. Nevertheless, results of studies in other species make it prudent and reasonable to believe that exposure of human germ cells to ionizing radiation and certain chemicals will cause mutations that will ultimately result in illness. The proliferation of test systems for mutagens in nonhuman species does not obviate but, in fact, presses the need for a demonstration of environmentally induced germinal mutation in human beings. Guidelines for protection from ionizing radiation in human beings have been largely extrapolated from observations in mice yet, the largest study of human populations exposed to a known mutagen of animals has, to date, shown that man may be more resistant than mice to genetic damage caused by the atomic bombs in Japan. The demonstration of what would seem an obvious biological conclusion - that what causes mutations in nonhuman species causes mutations in man - has been called ''one of the most difficult epidemiological issues ever faced by biomedical science''. Possible strategies have been considered repeatedly since the 1950s. At present, several large projects are under way to monitor certain manifestations of genetic damage, and formal protocols have been developed. Because the hazards of potential mutagens are world-wide and because it is difficult to gather sufficient number of exposed persons to detect significant changes in mutation rates, a WHO consultant group is developing protocols that, if accepted internationally, may provide answers

[en] This chapter describes the further development of Escherichia Coli K-12/343/113 as a multi-purpose indicator strain to be used in various mutagenicity testing procedures. In the subsequent improvements of its detecting capacity for mutagens and carcinogens, emphasis was put on the construction of derivatives with altered DNA dark repair ability on broadening the range of genes and gene loci under study, and on the establishment of optimal experimental conditions for phenotypic expression of induced mutants. In addition, liquid suspension tests were further developed, in which experimental conditions could be easily varied and monitored before, during and after treatment with the chemical substance under test, with concomitant determination of DNA dose, e.g. by using radioactively labelled chemicals. The final aim of these studies was the establishment of experimental protocols which could be used in quantitative interspecies comparisons of induced mutagenesis

[en] Studies of physically or chemically induced mutability (or revertibility) of viruses have aided the understanding of repair processes both in bacteria and in mammalian cells. Others first showed that UV-irradiated lambda phage underwent far more mutagenesis when infecting UV-irradiated E. coli host cells than when infecting non-irradiated hosts. This finding was indispensable to the concept of S.O.S. or error-prone repair and was, at least in part, responsible for the current interest in the biological and biochemical functions of the E. coli recA gene product and the regulatory system of which it is a part. Work along similar lines in mammalian cells, represents the extension of such research to mammalian cells. Systematic studies of UV-produced mutagenesis or reversion among nuclear-replicating double-stranded DNA mammalian viruses have been reported in SV40, their herpes viruses and adenoviruses. In this chapter the authors describe their methods for adenovirus 5

[en] Studies on exposed individuals, and on cultured cells, have shown that the human peripheral blood lymphocyte is an extremely sensitive indicator of both in vivo and in vitro induced chromosome structural change. These changes in chromosome structure offer readily scored morphological evidence of damage to the genetic material. Although problems exist in the extrapolation from in vitro results to the in vivo situation, the lymphocyte offers several advantages as a test system. The types of chromosome damage which can be cytologically distinguished at metaphase can be divided into two main groups: chromosome type and chromatid type. The circulating lymphocyte is in the G/sub 0/ or G/sub 1/ phase of mitosis and exposure to ionising radiations and certain other mutagenic agents during this stage produces chromosome-type damage where the unit of breakage and reunion is the whole chromosome (i.e. both chromatids at the same locus). However, cells exposed to these agents while in the S or G/sub 2/ stages of the cell cycle, after the chromosome has divided into two sister chromatids, yield chromatid-type aberrations and only the single chromatid is involved in breakage or exchange. Other agents (e.g. some of the alkylating agents) will usually produce only chromatid-type aberrations in cells in cycle although the cells are exposed to the mutagen whilst in G/sub 1/

[en] The handling of mutagenic chemicals should not only aim at the safety of personnel. Measures have also to be taken to prevent misleading experimental results through the use of defective chemicals. Usually the biologist has to accept that analytical data and/or degree of purity correspond to the statement on the bottle of a purchased chemical (although, in the case of labile chemicals, he is certainly justified to request a dated analytical attest). Especially many electrophilic reagents (alkylating, arylating, acylating, etc., agents) are so reactive that improper handling may lead to their deterioration, with the effect that the intended chemical has partly or wholly disappeared when the test is done. Evidently, decay of a chemical may take place during storage, but, in addition, the decomposition in the prepared test solution before it is used has to be considered. For the latter reason, some knowledge of the stability of chemicals in solution is required, in order to safeguard that sufficiently fresh solutions of reactive chemicals are used. Isotope-labelled mutagenic compounds represent, because of radiolytic decomposition, a special problem. Although this is outside the scope of the present chapter, the authors feel it justified to stress the necessity of extreme care to safeguard radiochemical purity at the time of delivery and at the time of use