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R C Woodruff

Publications and source records attributed to R C Woodruff.

At least 55 records · Page 3Linked to original sources

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↗

Interaction between mobile DNA-element-induced lethal mutations and chemical mutagens in the hybrid dysgenic system of Drosophila melanogaster.

Using the sex-linked recessive lethal mutation screen, a synergistic interaction is observed for mutations induced by chemical mutagens (ethyl methanesulfonate and dimethylnitrosamine) and the transposable DNA-element system of hybrid dysgenesis in spermatogonial cells of Drosophila melanogaster. Although the mechanism of this interaction is unknown, these results suggest that some chemical mutagens may induce transpositions, hybrid dysgenic cells may be more sensitive to chemically induced genetic damage, or hybrid dysgenesis may inhibit the efficiency of repair of chemically induced lesions.

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↗

The induction of chromosome aberrations by cis-platinum(II) diamminodichloride in Drosophila melanogaster.

We have determined the in vivo effects of cis-platinum(II)diamminodichloride (cis-PDD) treatment on the induction of chromosome aberrations in Drosophila melanogaster germ cells. cis-PDD treatment induces significant increases in chromosome breakage in all stages of spermatogenesis in a battery of test systems using ring or rod-X males and repair-proficient or deficient females. Since no increase in nondisjunction was induced by cis-PDD in either male or female germ cells, any aneuploidy inducing effects of this compound should result from its clastogenic action. We also find that mei-9 excision repair function is involved in the repair of cis-PDD-induced DNA lesions in a manner that provides additional evidence that partial and ring chromosome losses are not completely homologous.

Animals↗

Pesticide-induced complete and partial chromosome loss in screens with repair-defective females of Drosophila melanogaster.

Commercial preparation of fungicides (captan and maneb), herbicides (bromacil, paraquat, picloram, and 2,4-D), and insecticides (carbaryl, chlorpyrifos, dimethoate, DDT, diazinon, carbofuran, and permethrin) were tested for their ability to induce complete and partial chromosome losses in Drosophila melanogaster males. In an attempt to identify the mutagenic activity of pesticides that are toxic in low concentrations in Drosophila, these males were mated with mus-302 repair-defective females. The rationale for this mating scheme is based on the repair of genetic damage in Drosophila sperm by maternal enzymes in the zygote, and on the reports that there may be increases in the frequency of recovery of chemically induced chromosome losses in crosses of treated males with mus-302 females. Verification of the sensitivity of this screen in this study came from significant increases in the frequency of chromosome loss induced by low concentrations of the positive controls, N-nitrosodimethylamine and methyl methanesulfonate. Of the 13 pesticides, the insecticide chlorpyrifos induced a significant amount of ring-X chromosome loss. No pesticide induced a significant increase in partial chromosome loss. These results are discussed in relation to the usefulness of repair-defective mutants in screens for genetic damage in Drosophila and other higher eukaryotes by chemicals that are toxic or cause sterility at low concentrations.

Animals↗

The genetics of a small autosomal region of Drosophila melanogaster containing the structural gene for alcohol dehydrogenase. VI. Induced revertants of scutoid.

Twenty-six induced revertants of Scutoid (Sco), a dominant mutation of Drosophila melanogaster, have been characterized genetically. Sco is an unusual mutation, involving two small reciprocal transpositions within the region 35A4 to 35C5 of chromosome arm 2L. One of these transpositions juxtaposes the noc and l(2)br28 loci. We suggested previously that the Sco phenotype results from the "fusion" of noc and l(2)br28. In support of this idea we now show that 23 of 26 revertants of Sco are noc-, indeed the majority are either chromosome aberrations broken between noc and l(2)br28 or deletions of these loci from the mutant chromosome. However, some revertants of Sco are rather more complex, and their properties suggest an interaction between the pu-noc and l(2)br28-l(2)br37 regions of chromosome arm 2L and also demonstrate the genetic complexity of the el-noc region.

Alcohol Oxidoreductases↗

The genetics of a small chromosome region of Drosophila melanogaster containing the structural gene for alcohol dehydrogenase. IV: scutoid, an antimorphic mutation.

Exchange mapping locates the dominant mutation Scutoid to the right of Adh on chromosome arm 2L of D. melanogaster. However, deletion mapping indicates that Sco is to the left of Adh. The phenotype of Sco is sensitive to mutation, or deletion, of noc+ and of three genes, el, l(2)br22, and l(2)br29 mapping immediately distal to noc. The four contiguous loci, el, l(2)br22, l(2) br29 and noc, although separable by deletion end points, interact, because certain (or all) alleles of these four loci show partial failure of complementation, or even negative complementation. The simplest hypothesis is that Sco is a small reciprocal transposition, the genes noc, osp, and Adh exchanging places with three genes normally mapping proximal to them: l(2)br34, 1(2)br35 and rd. The Sco phenotype is thought to result from a position effect at the newly created noc/l(2)br28 junction.

Alcohol Oxidoreductases↗

Genetic factors that affect rates of spontaneous mutation and chromosome aberrations in Drosophila melanogaster.

Several important human syndromes provide evidence for the idea that the rate of gene mutation and chromosome breakage is under genetic control. Although not understood in detail, their underlying mechanisms include deficiencies in DNA replication, repair, and increased sensitivity to external agents. The ease of genetic analysis in Drosophila melanogaster offers a number of model systems that may give useful insights into comparable human conditions. For example, some of the many meiotic mutants isolated from natural populations provide information on the genetics of DNA repair in a eukaryote. In addition, complex syndromes affecting mutation rate are available for study. One such system is hybrid dysgenesis in Drosophila. Hybrid dysgenesis refers to a collection of genetic changes, including chromosome breakage, increased mutation rates, and sterility expressed in crosses between independent population lines. Our recent work has focused upon chromosome breakage and mutator activity in this system. The pattern of inheritance and expression of mutator activity implicates a chromosome-cytoplasm interaction for its induction. Furthermore, the genetic elements responsible for this phenomenon appear to move from one location or chromosome to another. Indeed, one can draw a convincing parallel between hybrid dysgenesis and the behavior of transposable, or nomadic, DNA sequences. Thus, one must view the phenotype "mutation rate" as a conglomerate of factors affecting DNA stability, physiological condition, and the behavior of genetic elements.

Animals↗

A model for spontaneous mutation in Drosophila caused by transposing elements.

Transposing genetic elements make up a significant proportion of the DNA of at least some eukaryotes. One of the potential side effects of transposition is a high rate of apparently spontaneous mutation. In this paper we consider some of the evolutionary strategies that might be involved in the suppression of transposition, and we outline a model for the control of spontaneous mutation in terms of the regulation of transposition. Specific predictions are based upon the well-characterized genetics of the mutator system associated with hybrid dysgenesis in Drosophila melanogaster, which has many parallels with the expected behaviour of transposing elements.

Animals↗

Increased mutation in crosses between geographically separated strains of Drosophila melanogaster.

Mutator activity associated with the common male recombination (MR) chromosomes in Drosophila melanogaster appears to be suppressed in natural populations. Crosses between geographically separated populations, however, lead to the release of mutator activity as measured by a significant increase in visible mutations. Such an increase in mutation in hybrid individuals may be a powerful factor in inducing or releasing variation in nature, and in more extreme instances may contribute to the separation of microdifferentiated populations.

Animals↗