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The Salmonella assay has been in use for almost 15 years and can be defined as a routine test for mutagenicity and for predicting potential carcinogenicity. It detects the majority of animal carcinogens and consequently plays an important role in safety assessment. The test is also routinely used as the frontline screen for environmental samples (complex mixtures) isolated from air, water and food. This role will continue to remain an area of growth as or because sample volumes associated with these testing areas are generally very limited and more extensive testing is generally impossible. While this test, like all others, has some limitations, it is recommended that it be regularly included in all genetic testing batteries.

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The term 'chromosome mutations' was chosen and defined for this review to refer to alterations of chromosome structure (reciprocal, heritable translocations), of chromosome number (loss or gain of a whole chromosome), or of chromosome content (loss or gain of a part of a chromosome). Chromosome mutations may result from chromosome breakage (clastogenesis) and its consequences or from disruption of chromosome behavior during cell division (nondisjunction). State-of-the-art protocols are outlined to test for heritable translocations, for whole-or partial chromosome loss (clastogenesis), and for whole chromosome loss or gain (nondisjunction). The literature up to 1980 was reviewed and 106 papers were selected for the evaluation of 116 chemicals for one or more chromosome mutation end points. The criteria used for acceptance of data from the literature were not stringent, as most of this work was done some time ago and for purposes other than testing. The main criterion was that germ cell stage sampling was correct. For the evaluation of the accepted data, numerical requirements were set up, using as a guide the control data from all the papers. Compounds were classified, when possible, as mutagenic (+) or nonmutagenic (-). Those not classifiable, usually due to insufficient numbers of chromosomes tested, were listed as inconclusive (inc). Of 61 compounds tested for heritable translocations, 27 were positive, 8 were negative, and 26 were inconclusive. Of the 35 with conclusive data, only 21 also have definitive carcinogenesis classifications (all positive). Of these, 19 were deemed mutagenic, which gives agreement of 90.5%. Of the 76 compounds tested for clastogenesis by the chromosome loss test, 26 were positive, 13 were negative, and 37 were inconclusive. Of the 39 with conclusive data, only 20 also have definitive carcinogenesis classifications. 15 of the 19 carcinogens were positive. Four of the carcinogens were negative and 1 noncarcinogen was positive, for an overall agreement of 75%. Of 44 compounds tested for nondisjunction, 15 were positive, 13 were negative, 16 were inconclusive. Of the 28 compounds with conclusive data, only 9 have definitive carcinogenesis classifications (all positive). Five of these were deemed negative and agreement was only 44%. It should be noted that these data do not fairly represent these short-term tests as conducted with current protocols. A more equitable comparison could be achieved with planned experiments that include the sex-linked recessive lethal (SLRL) test in the comparison.

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The yeast Saccharomyces cerevisiae is a unicellular fungus that can be cultured as a stable haploid or a stable diploid . Diploid cultures can be induced to undergo meiosis in a synchronous fashion under well-defined conditions. Consequently, yeasts can be used to study genetic effects both in mitotic and in meiotic cells. Haploid strains have been used to study the induction of point mutations. In addition to point mutation induction, diploid strains have been used for studying mitotic recombination, which is the expression of the cellular repair activities induced by inflicted damage. Chromosomal malsegregation in mitotic and meiotic cells can also be studied in appropriately marked strains. Yeast has a considerable potential for endogenous activation, provided the tests are performed with appropriate cells. Exogenous activation has been achieved with S9 rodent liver in test tubes as well as in the host-mediated assay, where cells are injected into rodents. Yeast cells can be recovered from various organs and tested for induced genetic effects. The most commonly used genetic end point has been mitotic recombination either as mitotic crossing-over or mitotic gene conversion. A number of different strains are used by different authors. This also applies to haploid strains used for monitoring induction of point mutations. Mitotic chromosome malsegregation has been studied mainly with strain D6 and meiotic malsegregation with strain DIS13 . Data were available on tests with 492 chemicals, of which 249 were positive, as reported in 173 articles or reports. The genetic test/carcinogenicity accuracy was 0.74, based on the carcinogen listing established in the Gene-Tox Program. The yeast tests supplement the bacterial tests for detecting agents that act via radical formation, antibacterial drugs, and other chemicals interfering with chromosome segregation and recombination processes.

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The utility of unscheduled DNA synthesis (UDS) testing for screening potentially hazardous chemicals was evaluated using the published papers and technical reports available to the UDS Work Group. A total of 244 documents were reviewed. Based on criteria defined in advance for evaluation of the results, 169 were rejected. From the 75 documents accepted, results were reviewed for 136 chemicals tested using autoradiographic approaches and for 147 chemicals tested using liquid scintillation counting (LSC) procedures; 38 chemicals were tested by both approaches to measure UDS. Since there were no documents available that provided detailed recommendations of UDS screening protocols or criteria for evaluating the results, the UDS Work Group presents suggested protocols and evaluation criteria suitable for measuring and evaluating UDS by autoradiography in primary rat hepatocytes and diploid human fibroblasts and by the LSC approach in diploid human fibroblasts. UDS detection is an appropriate system for inclusion in carcinogenicity and mutagenicity testing programs, because it measures the repair of DNA damage induced by many classes of chemicals over the entire mammalian genome. However, for this system to be utilized effectively, appropriate metabolic activation systems for autoradiographic measurements of UDS in human diploid fibroblasts must be developed, the nature of hepatocyte-to-hepatocyte variability in UDS responses must be determined, and the three suggested protocols must be thoroughly evaluated by using them to test a large number of coded chemicals of known in vivo mutagenicity and carcinogenicity.

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The test for sex-linked recessive lethals (SLRL) in Drosophila melanogaster has been used to detect induced mutations since 1927. The advantage of the test for both screening and hazard evaluation is its objectivity in testing for transmissible mutations in the germ cells of a eukaryote. Statistical criteria for both positive and negative mutagenicity at the highest concentration tested under a particular exposure condition were developed by the Work Group, and a recommended protocol for future testing was agreed upon. For 421 compounds there were sufficient data available in the literature for analysis; 198 compounds were found to be positive and 46 negative at the highest concentration tested. Most experiments had been done for objectives of pure research rather than for deliberately screening for mutagenicity, although many of the 421 chemicals were selected for testing because of suspected mutagenicity. Therefore, the statement of 198 positive and 46 negative should not be taken as an example of the proportion of mutagens in the environment. In three sets of experiments with D. melanogaster that were done specifically for screening, one involving 40 compounds for the Environmental Protection Agency (EPA), the others involving 13 for the Food and Drug Administration (FDA), only 6 mutagens were discovered. After completion of the classification of compounds according to their response in the SLRL test, the compounds were classified as to their carcinogenic response according to the list of Griesemer and Cueto (1980). There were 62 compounds that could be classified as positive or negative for both carcinogenesis and mutagenesis. Of the 62 compounds, there was agreement between the carcinogenesis and mutagenesis classification in 56 (50 positive and 6 negative), or 90% would have been correctly classified as to carcinogenesis from only the SLRL test. Because of inadequate sample size, 177 compounds could not be classified as positive or negative according to the statistical criteria established by the Work Group. This large number of inadequately tested compounds reflects the fact that many of the experiments were not done for screening. Further work is needed on the compounds with inadequate sample size.(ABSTRACT TRUNCATED AT 400 WORDS)

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Two genetic end-points are used for testing mutagens in Schizosaccharomyces pombe: forward mutations of the loci which encode steps early in the adenine synthetic pathway and reversion of certain selected mutants. 54 chemicals have been tested for at least one of the genetic end-points. The relevant literature has been reviewed through 1979.

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Literature reports were surveyed, with results noted from experiments in seven nonmammalian assay systems used for the detection of mutagenicity or other related genetic effects. A comparison was made of the activities of 54 selected noncarcinogens, procarcinogens, and ultimate carcinogens as revealed by these test systems. Of the compounds tested, 49 (91%) were active in one or more of the assays, and 42 (78%) were positive in at least one system without having to be metabolically activated. In one or more test systems, 17/17 (100%) of the ultimate carcinogens, 27/28 (96%) of the procarcinogens, and 6/9 (67%) of the noncarcinogens were positive. The Ames Salmonella-microsome assay responded with increased mutation frequency to 37/44 (84%) of the carcinogenic compounds but to only 2/8 (25%) of the noncarcinogens tested. The Drosophila system responded to 19/21 (90%) of the carcinogens and to 3/6 (50%) of the noncarcinogens. Prophages were induced when lysogenic bacteria were exposed to 12/21 (57%) of the carcinogens, but not enough tests were done with the noncarcinogens (1/3, or 33%) for a comparison. The other systems reviewed, such as the killing of repair-deficient bacteria, mutations in Escherichia coli and Neurospora crassa, and the host-mediated assay, were not challenged by enough of the compounds for valid comparisons.

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