Drosophila Test

LED, lowest effeetive dose HID, highest ineffeetive dose in-vitro tests, p,g/mL in-vivo tests, mg/kg bw/day Drosophila tests, ppm po, oral ip, intraperitoneal... 

In answer to the first question, the Committee suggests a two-tier system of inexpensive, short-term, sensitive mutagenicity tests that could be widely applied to identify substances that may represent a mutagenic hazard. The first tier uses one microbial test and two mammalian cell-culture tests. If the results of this tier are inconclusive, a Drosophila test (the second tier) is used. If the results are still insufficient for a manufacturing or control decision, further tests cure available, including those using mice. The test scheme is presented later in this summary and in more detail in Chapter 9. 

The classical mutation tests in Drosophila use special strains that detect recessive lethal mutations on the X chromosome. They have the advantage that mutations at all lethal-producing loci on the chromosome, and not just those at a few selected loci, are detected. Various germ cell stages can be tested in both sexes. There are also tests for chromosomal breakage and rearrangement. These Drosophila tests require a few weeks. 

If this is positive, the chemical is classified as a presumed mammalian mutagen if negative, the chemical is a presumed mammalian nonmutagen. An examination of 36 mutagenic chemicals in which several of these tests had been done showed that at least 31 would have been identified by Tier I tests alone. This suggests that the more expensive Drosophila tests would not be needed for most chemicals. 

Examination of Groups A and B shows that in the overwhelming majority of these cases a decision would have been reached on the basis of Tier I tests alone. The more expensive Drosophila tests would not be needed most of the time. Note, however, that the collection of chemicals in Table 9-3 is biased in favor of definite and strong mutagens, because these are more fully represented in the literature. 

Fluothane was negative in two Tier I tests (and not subjected to the third), but was positive in the Drosophila test. If fluothane had also had a negative result in the mammalian cytogenetic test, it would be the only example in this series of a substance that was mutagenic according to the Tier II test but was not detected in Tier I. 

Captan had one ambiguous result and one positive result in the two Tier I tests used. It was also positive in the, mouse dominant-lethal test. Because results in the Drosophila test were negative, captan is a doubtful mutagen that requires more testing. 

There are no quick, inexpensive, sensitive, and validated tests for aneuploidy. Fungal tests are being developed, and Drosophila tests are being validated. X-chromosome aneuploidy can be detected in the mouse, but the test is too expensive for general use. The detection of XX, XX, and YY spermatids in the vole appears promising, but a test system has not been developed for routine use. 

Short-term tests are receiving favorable consideration in many laboratories. The report of Stoltz al. and other experts in the field conclude that tests involving mutagenicity (point mutations, DNA damage, chromosome changes as shown by Ames, micronucleus, mouse lymphoma. Drosophila tests), DNA repair synthesis and cell transformation offer promise as screens for carcinogens. 

Tripathy NK, Dey L, Majhi B, et al. 1987. Genotoxicity of metacid established through the somatic and germ line mosaic assays and the sex-linked recessive lethal test in drosophila. Arch Toxicol 61 53-57. 

Insect systems Drosophila melanogaster (sex-linked recessive lethal test) Recessive lethal mutation + Velazquez et al. 1984... 

The most dramatic illustration of the evolutionary conservation of homeobox genes comes from experiments that swap Drosophila and mammalian cognates and test for functional equivalence. McGinnis and co-workers have reported remarkable phenotypic similarities in flies that misexpress Drosophila homeobox genes or their mammalian counterparts. Indeed, this ectopic expression assay in Drosophila indicates that the Drosophila and cognate mammalian homeobox proteins are essentially functionally identical. 

Fujikawa K, Ryo H, Kondo S. 1985. The Drosophila reversion assay using the unstable zeste-white somatic eye color system. In Ashby J, de Serres FJ, et al., eds. Progress in mutation research. Vol. 5. Evaluation of short-term tests for carcinogens. Amsterdam, The Netherlands Elsevier Science Publishers, 319-324. 

The role of CREB in learning and memory was first anticipated by screening Drosophila mutants in a learning and memory task in which flies were behaviorally tested... 

When simple substances, even those that are intimately associated with living processes, are tested upon organisms, the results may be highly variable depending on the genetics of the organism tested. Thus, there are strains of Drosophila which are sensitive and resistant, respectively, to carbon dioxide. Some can stand hours of contact with pure carbon dioxide without permanent injury, while others either do not recover from the narcosis or, if they do, their movements... 

Crespi et al. 1985 Ferrari et al. 1983 Mailing 1969 Principe et al. 1981 Tan and Hsie 1981). It has been tested for its ability to induce heritable mutations in vivo using fruit flies (Drosophila melanogaster), mice, and rats. 1,2-Dibromoethane caused heritable mutations in male fruit flies (Kale and Baum 1979, 1981, 1982, 1983 Vogel and Chandler 1974) but not in mice (Epstein et al. 1972 Teramoto et al. 1980) or rats (Teramoto et al. 1980). 

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