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S Zimmering

Publications and source records attributed to S Zimmering.

At least 37 records · Page 2Linked to original sources

Aneuploidy in Drosophila. III: Aneuploidogens inhibit in vitro assembly of taxol-purified Drosophila microtubules.

The in vitro effects of aneuploidogens on taxol-purified microtubules from whole Drosophila melanogaster and mouse brain were studied by a spectrophotometric assay and electron microscopy. Colchicine, acetonitrile, propionitrile, acrylonitrile, dimethylsulfoxide (DMSO), griseofulvin, and cadmium chloride inhibit microtubule assembly, whereas methoxyethyl acetate (MEA) does not. Qualitatively similar results were observed with D. melanogaster and mouse brain microtubules. The in vitro results from D. melanogaster correlate well with previously published results from in vivo assays monitoring induced sex chromosome aneuploidy in that effective aneuploidogens are observed to affect microtubule assembly. The inclusion of taxol does not appear to qualitatively affect the assembly assays with the chemicals tested. In contrast with results from assembly assays, the tested aneuploidogens, including colchicine, do not promote disassembly to taxol-purified microtubules. It is possible that taxol has shifted the equilibrium and stabilized the formed microtubules to the extent that they are no longer sensitive to aneuploidogen-induced disassembly.

Acetates↗

Aneuploidy in Drosophila, I. Genetic test systems in the female Drosophila melanogaster for the rapid detection of chemically induced chromosome gain and chromosome loss.

An account is provided of two genetic schemes in the Drosophila melanogaster female designed as rapid detectors of chemically induced aneuploidy, including both chromosome gain and chromosome loss. One scheme is referred to as FIX, in which the female carried free (heterozygously) inverted X (chromosomes) and the other, ZESTE, where females do not carry inversions and the X-linked sexually dimorphic zeste mutation plays the key role in the detection of aneuploid offspring. The principle attribute of the FIX system is that all euploid offspring are wild-type for body and eye color whereas aneuploid females have a yellow body and aneuploid males white eyes; int he ZESTE system all euploid individuals are wild-type for eye color, aneuploid females possess zeste-colored eyes and aneuploid males white eyes. In addition induced polyploidies (2X:2A gametes) appear as yellow and zeste male intersexes in the FIX and ZESTE systems, respectively. In this way all aneuploids are recognized immediately. Consequently, detection of compounds with weak effects requiring large sample sizes may be made in a fraction of the time associated with more traditional schemes for aneuploidy detection in Drosophila.

Aneuploidy↗

Chemical mutagenesis testing in Drosophila. VI. Interlaboratory comparison of mutagenicity tests after treatment of larvae.

Previous publications on the National Toxicology Program (NTP)-sponsored mutagenicity testing program in Drosophila dealt with evaluations of chemicals following adult treatment (feed, injection). The current paper deals with a comparison between the laboratories at Brown University (BRU) and the University of Wisconsin at Madison (UWM) regarding the response of larvae to treatment with chemicals in the sex-linked recessive lethal (SLRL) test and, where appropriate, the reciprocal translocation test as well. Dimethylnitrosamine (DMN) and dimethylbenz(a)anthracene were used first as reference mutagens. Six coded compounds were then evaluated regarding their repeatability in the two laboratories; the compounds were benzo(a)pyrene, 3-methylcholanthrene, coumarin, quinoline, formaldehyde, and 9-aminoacridine. It was concluded that at this time it would be imprudent to forgo larval treatment in cases where compounds proved negative after adult feeding. Accordingly, testing a series of 20 compounds negative after adult treatment is in progress.

9,10-Dimethyl-1,2-benzanthracene↗

Chemical mutagenesis testing in Drosophila. II. Results of 20 coded compounds tested for the National Toxicology Program.

Results are presented from mutagenesis testing in Drosophila of 20 coded compounds. Two compounds were positive in the sex-linked recessive lethal test, and two were inconclusive. The positive compounds were calcium chromate in adult feeding experiments and ferrocene after adult injection. The two inconclusive compounds were 2,4-diaminophenol dihydrochloride and hexachlorocyclopentadiene. Compounds that produced a positive response were assayed for chromosome breakage using the conventional translocation test. Calcium chromate was negative in the translocation test, and ferrocene was positive. Many of the test compounds were poorly soluble in water, raising questions regarding the effective concentration to which the flies were exposed.

Animals↗

Chemical mutagenesis testing in Drosophila. III. Results of 48 coded compounds tested for the National Toxicology Program.

Forty-eight chemicals were tested for mutagenicity in Drosophila melanogaster. Each compound was tested first for the induction of sex-linked recessive lethals (SLRLs) by feeding the chemical in a solution of 5% aqueous sucrose. If it was not mutagenic by this route, the chemical was tested by injection in a solution of 0.7% aqueous NaCl. If found inactive, the compound was not tested further. If it was mutagenic, the compound was tested for the induction of reciprocal translocations (RTs) using the exposure protocol and germ cell stage that yielded positive results in the SLRL assay. Eight chemicals (diglycidylresorcinol ether, AF-2, alloxan monohydrate, 1-aziridine ethanol, p,p'-DDE, dichloroacetonitrile, 1,3-dichloropropene, and 3,3'-dimethylbenzidine dihydrochloride) were found to induce SLRLs. Only diglycidylresorcinol ether also induced RTs.

Animals↗

Chemical mutagenesis testing in Drosophila. IV. Results of 45 coded compounds tested for the National Toxicology Program.

Results from Drosophila mutagenicity tests of 45 chemical compounds assayed for the National Toxicology Program are presented. Nine compounds were judged positive and four equivocal in the sex-linked recessive lethal test. The nine positive compounds were acetin, allyl glycidyl ether, cyclophosphamide, 1,2-dibromo-3-chloropropane, 2,3-dibromo-1-propanol, dimethylcarbamyl chloride, 1,2-epoxy-butane, lasiocarpine, and N-nitrosopiperidine. The results for chloral hydrate, maleic hydrazide, propantheline bromide, and trifluralin were equivocal. Of the nine compounds positive in recessive lethal induction, only two--allyl glycidyl ether and dimethylcarbamyl chloride--failed to induce translocations. The remaining 32 were judged to be nonmutagenic under the conditions used.

Animals↗

Genetic drift and seasonal variation in spontaneous mutation frequencies in Drosophila.

Spontaneous sex-linked recessive lethal mutation frequencies may vary with time. Examination of approximately 1.7 X 10(6) Drosophila melanogaster X chromosomes in three laboratories suggests two sources of variation in the spontaneous mutation frequency. First, the underlying mutation rate may change with time, suggesting genetic drift among the genes controlling the spontaneous mutation rate. In one set of experiments, the recessive lethal frequency increased from 0.2% to 0.4% in 6 years. Second, there may be seasonal variation in the mutation frequency even under apparently controlled conditions, suggesting that uncontrolled environmental factors may play an important role in determining the mutation frequency. Therefore, concurrent controls should be used in mutation experiments except in cases in which the frequency in the untreated control is so low as to be unmeasurable in a single experiment or the control frequency can be shown not to vary with time.

Animals↗

Chemical mutagenesis testing in Drosophila. V. Results of 53 coded compounds tested for the National Toxicology Program.

Fifty-three chemicals were tested for mutagenicity in Drosophila melanogaster by adult feeding and, where results were negative, by adult injection for the induction of sex-linked recessive lethal mutations in meiotic and postmeiotic germ cell stages of Canton-S males. One compound was tested by inhalation. Those compounds that induced lethal mutations were tested further for the induction of reciprocal translocations. Seventeen of the 53 compounds (acetaldehyde, 2-aminoanthracene, bromoform, t-butyl hydroperoxide, chlorambucil, trans-cinnamaldehyde, crotonaldehyde, 1,3-dichloro-5,5-dimethylhydantoin, 3,4-dichloronitrobenzene, dimethoxane, 2,4-dinitrotoluene, 1,2-epoxy-3,3,3-trichloropropane, formaldehyde, furfural, halothane, HC yellow 4, and picric acid) were found to induce lethal mutations and three (2-aminoanthracene, chlorambucil,and crotonaldehyde) also induced reciprocal translocations.

Animals↗

Chemical mutagenesis testing in Drosophila: I. Comparison of positive and negative control data for sex-linked recessive lethal mutations and reciprocal translocations in three laboratories.

As part of the validation phase of the Drosophila melanogaster segment of the National Toxicology Program, a comparison has been made of positive and negative controls for sex-linked recessive lethal mutations and reciprocal translocations from three laboratories. This comparison involves approximately 700,000 spontaneous recessive lethal mutation tests, 70,000 spontaneous translocation tests, and screens for genetic damage induced by N-nitrosodimethylamine and beta-propiolactone. Spontaneous frequencies for lethal mutations and translocations were homogeneous in the laboratories regardless of solvent or broods sampled. Inhomogeneity was observed in induced frequencies among laboratories, but the variation was no greater than that found within a laboratory.

Animals↗

Chromosome mutation tests for mutagenesis in Drosophila melanogaster. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

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.

Aneuploidy↗