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Biomedical subjects

S Zimmering

Publications and source records attributed to S Zimmering.

At least 55 records · Page 3Linked to original sources
PubMed1983

The mei-9a test for chromosome loss in Drosophila: a review of assays of 21 chemicals for chromosome breakage.

In Drosophila, detection of chemical-induced chromosome breakage for many compounds in conventional chromosome loss or reciprocal translocation (RT) tests requires considerably higher concentrations than for sex-linked recessive lethals, or fails entirely even at concentrations giving substantial to high rates of recessive lethals. Accordingly, relatively high LDs may be necessary before evidence of chromosome breakage is observed raising questions of "false positives" resulting, for example, from aberrant metabolic effects/products not found at lower concentrations. In the test for chromosome loss, definitive scoring is made in F1 progeny. In contrast, an F2 and often an F3 is required to bring the RT test to completion. Further, the RT test is prone to "false negatives" in many cases unless testing is carried out on sperm stored in the female for several days (or longer). Accordingly, efforts in this laboratory have been directed toward improvements in the sensitivity of the test for chromosome loss. Major advances have been made by using excision repair deficient mei-9a females as P1 females to which treated males are mated. For purposes of testing, ring-X males carrying the doubly marked Y chromosome, BSYy+, were treated or not, mated for 3 days with ordinary (repair-proficient) females (the conventional test) or with mei-9a females (the mei-9a test) and all P1s discarded. Data are reported for this period only--viz, on unstored sperm. F1 progeny were scored for complete loss (CL) of the X or Y (loss is principally of the ring-X) and partial loss of the Y (PL)--viz, loss of BS or y+. Partial loss of the Y chromosome was taken as strong evidence of chromosome breakage, whereas loss of the ring-X was regarded alternatively as break-related or resulting from the production of sister chromatid exchanges. Of the 21 compounds tested, 17 are classified as carcinogens and four are unknown in this regard. At the concentration reported, 21/21 compounds were positive for CL+PL and 21/21 for PL in the mei-9a test. At the same concentration, only 10/20 compounds were positive for CL and PL and 2/21 compounds for PL with repair proficient females; the mei-9a test is clearly more sensitive than the conventional test for chromosome breakage.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1983

The sex-linked recessive lethal test for mutagenesis in Drosophila melanogaster. A report of the U.S. Environmental Protection Agency Gene-Tox Program.

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)

Animals↗
PubMed1982

Induced chromosome loss following treatment of postmeiotic cells of the Drosophila melanogaster male with MMS and DMN and matings with repair-proficient females and the repair-deficient females mei-9a and st mus302.

Drosophila melanogaster ring-X males carrying a double marked Y chromosome, BsYy+, were treated with MMS or DMN and mated with repair-proficient females or the repair-deficient females mei-9a and st. mus302. Frequencies of induced complete loss (principally the ring-X) and partial losses of the Y chromosome (loss of Bs or Y+) decreased in the sequence st must302 greater than mei-9a greater than repair-proficient females agreeing with the sequence obtained previously with procarbazine and DEN. With MMS and DMN, some 30-40% or more or partial Y chromosome losses are mosaics from mei-9a and only 0.4% from st mus302 females and a delay in mei-9a females. Similar findings with procarbazine and DEN are indicated. That the higher sensitivity of st mus302 relative to mei-9a results from impairments in both postreplication and excision repair in the former remains to be determined.

Aneuploidy↗
PubMed1981

Review of the current status of the mei-9a test for chromosome loss in Drosophila melanogaster: an assay with radically improved detection capacity for chromosome lesions induced by methyl methanesulfonate (MMS), dimethylnitrosamine (DMN), and especially diethylnitrosamine (DEN) and procarbazine.

A review of previous findings as well as new data are included in the present paper on recent investigations by Zimmering and co-workers regarding a radical improvement in the detection capacity of the conventional test for chromosome loss to assay for induced chromosome lesions/breakage. The improvement has been achieved through the use of mei-9a repair-deficient P1 females to which treated males are mated. 4 compounds have been tested including MMS, DMN, DEN and procarbazine. Not only has the mei-9a test yielded significantly higher frequencies of induced chromosome loss with MMS and DMN than the conventional test, preliminary data, in fact, providing evidence of a positive response in the mei-9a test at a concentration one order of magnitude below that producing no effect in the conventional test, but, more critically, it has permitted detection of highly significant increases in induced chromosome loss with DEN and procarbazine, compounds proving negative in the conventional tests for chromosome loss and heritable translocations at all concentrations employed including those producing substantial to high frequencies of recessive lethals.

Animals↗
PubMed1981

A genetic study of the effects of the repair-deficient mei-9a mutation in Drosophila on spontaneous and X-ray-induced paternal sex chromosome loss.

The repair-deficient mutant, mei-9a in Drosophila melanogaster was investigated regarding its effect on spontaneous and X-ray-induced chromosome loss in male postmeiotic cells. From matings of males carrying a mei-9a or an ordinary ring-X and a doubly marked Y chromosome (BSYy+) with mei-9a or ordinary females, the spontaneous frequencies of complete loss, partial loss, and inferred ring-X loss (based on shifts in sex ratio female:male) were significantly higher with mei-9a than with non-mei-9a. When males were given 3000 rad X-irradiation, frequencies of induced partial loss, inferred ring-X loss and the reduction in the number of progeny per female were significantly greater with mei-9a than with non-mei-9a. The results provide evidence that the mei-9a is a potentiator of both spontaneous and X-ray-induced chromosome lesions in sperm of the Drosophila male. Evidence is presented which implicates the presence of mei-9a in the P1 female and not the male as (at least) largely responsible for the characteristic mei-9a effects.

Animals↗
PubMed1981

Genetic study on the effects of the repair-deficient mutant females mei-9a, mei-41D5, mus101D1, mus104D1 and mus302D1 of Drosophila on spontaneous and X-ray-induced chromosome loss in the paternal genome.

The repair-deficient mutants mei-9a, mei-41D5, mus101D1, mus104D1 and mus302D1 in Drosophila melanogaster were investigated regarding their effects on spontaneous and X-ray-induced chromosome loss in postmeiotic cells. Each mutant was incorporated singly into XC2, and the ring-X male provided with BSYy+. From matings of males carrying mus101D1, mus302D1 or mei-41D5, mutants identifying a caffeine-sensitive (CAS) postreplication-repair pathway, with corresponding mutant females, and non-mutant males to non-mutant females, overall frequencies of spontaneous partial loss and spontaneous complete loss were significantly increased in each mutant cross except for spontaneous complete loss with mus302 where an increase was noted only in brood 2. Similar findings were noted when males carrying the excision-repair mutant mei-9a were mated with mei-9a females. Males carrying the mutant mus104D1, identifying a caffeine-insensitive (CIS) postreplication-repair pathway, tested with mus104D1 females, produced results that were not significantly different from non-mutant controls. When males were given 3000 rad X-irradiation, frequencies of induced partial loss were significantly higher with mus101D1, mus302D1, mei-41D5 and mei91, and not significantly higher with mus101D1, mus302D1, mei41D5 and mei-9a, and not significantly different from controls with mus104D1. It was suggested that the functional CAS postreplication-repair pathway primarily promotes repair of breaks while an alternative pathway(s) not defined by mus104 promotes misrepair. Therefore, the significant increases in both spontaneous and induced partial loss with the excision-repair-deficient mutant mei-9a suggests the possibility that (a) the excision-repair-pathway may not function in misrepair and (b) the undefined misrepair pathway may be dominant pathway for postreplication repair in Drosophila since mei-9a females presumably have functional postreplication repair and misrepair capacity. The suggestion that the CAS postreplication-repair pathway and the excision-repair pathway function primarily in repair, and an undefined pathway in misrepair is in line with the finding that with mus104D1, no significant increase was found in spontaneous complete loss, but with mus101D1, mus302D1, mei-41D5 and mei-9a significant increases were observed. Results on induced complete loss, with the exception of those with mei-41D5, show a poor correlation with other classes of loss of each of the mutants. Possible explanations for this discrepancy are discussed.

Animals↗
PubMed1981

The repair-deficient mei-9 alpha Drosophila female potentiates chromosome loss induced in the parenteral genome by diethylnitrosamine.

Following matings of DEN-treated Xc2/BSYy+ males with repair-deficient mei-9 alpha females and ordinary females, significant increases in complete and partial sex chromosome loss as well as dramatic shifts in sex ratio were found with mei-9 alpha but not ordinary females. Accordingly, the mei-9 alpha female enhances the detection of chromosome lesions leading to chromosome loss induced in the male genome by DEN. To date, the 4 compounds tested in this way (DMN, DEN, MMS and procarbazine) exhibit strong potentiation of chromosome loss with mei-9 alpha females suggesting the possibility that a protocol involving treatment (or not) or Xc2/BSYy+ males mated with mei-9 alpha females may hold promise as an alternative to traditional tests for chromosome loss using repair-proficient females. Comparison with published translocation data on the 4 compounds indicated above suggests an overall greater sensitivity of the described mei-9 alpha chromosome-loss test compared with the traditional translocation test in the detection of chemically induced chromosome lesions.

Animals↗
PubMed1980

Evidence that the repair deficient mei-9a female in Drosophila melanogaster is a strong potentiator of chromosome loss induced in the paternal genome by dimethylnitrosamine.

From mating of Xc2/BsYy+ males treated or not with 2.5 mM DMN (dimethylnitrosamine) with repair-deficient mei-9a females or with ordinary females, induced frequencies of observed (recovered) chromosome loss were 3.69% and 0.65% and inferred (non-recovered) ring-X loss based on shifts in sex ratio (male male/female female) was 47.9% and 9.4%, respectively. Results indicate that the mei-9a female is a strong potentiator of DMN-induced chromosome damage in sperm and suggest that DMN-induced chromosome lesions are produced in substantially higher frequency in treated sperm than deducible after crosses with repair-efficient females.

Animals↗
PubMed1980

Potentiation of chromosome loss induced in the paternal genome by methyl methanesulfonate and procarbazine following matings with repair deficient mei-9a females of Drosophila.

Drosophila melanogaster males carrying a ring-X (Xc2) and a doubly-marked Y chromosome (BSYy+) were treated with methylmethane sulfonate (MMS) and procarbazine, and mated with repair-deficient mei-9a females or ordinary repair-proficient females. Observed (recovered) chromosome loss were scored and nonrecovered inferred. Ring-X loss based on shifts in sex ratio were noted. Results indicate that the mei-9a female is strong potentiator of chromosome loss induced by MMS and procarbazine in line with the effect recently shown for dimethylnitrosamine (DMN)-induced chromosome lesions (Zimmering, et al 1980).

Animals↗