Biomedical subjects
Publications and source records attributed to S Zimmering.
Evidence is presented supporting the suggestion that homozygosity for the repair-deficient mutants mei-9a mei-41D5 is associated with a maternal effect which affects detrimentally the recovery rate of Y chromosome-bearing offspring.
0-8 h old Drosophila females carrying a reversed metacentric X chromosome and a suitably marked Y chromosome were treated or not with 0.2% caffeine and irradiated with 2000 R X-rays. In contrast with the reduction found in translocation frequency following 2000 R irradiation of the male mated with 0.2% caffeine-treated females, the frequency of interchanges in oocytes was significantly higher with caffeine as compared with controls.
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Drosophila melanogaster females were treated with 1% caffeine, mated with X-rayed males and the frequencies of induced sex-chromosome loss, translocations between the major autosomes and between the Y-chromosome and the major autosomes determined. In a reversal of the results obtained previously with 0.2% caffeine by Mendelson and Sobels, treatment of females with 1% caffeine led to a decrease in sex-chromosome loss, confirming preliminary data of Zimmering and Osgood and an increase in autosome--autosome translocations. It is suggested that the higher concentration of caffeine inhibits replication permitting more time available for chromosome-type restitutions by means of caffeine-insensitive repair mechanisms. In contrast with results for autosome--autosome translocation, the frequency of Y-autosome translocations was depressed below controls suggesting an isolation (by any one of several means) of Y-chromosome breaks from those in the autosomes.
The narcotic antagonist, Naltrexone, was tested for mutagenicity in Drosophila. The frequency of sex-linked recessive lethals at a non-toxic dose of 10 mg/ml was 0.43% (42 lethals in 9697 X-chromosomes tested) and 0.16% (19/11536) in the controls. The difference is statistically significant (P less than 0.001). Results from large-scale experiments testing for chromosome breakage and nondisjunction were negative.
The compound, methadone, used as a modality in the treatment of heroin addiction, was tested for mutagenic activity in germ cells of Drosophila. Results were negative in tests for sex-linked recessive lethals using feeding and injection procedures. Similarly, results from tests for chromosome breakage and nondisjunction failed to provide evidence of a mutagenic effect.
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From crosses of females possessing a heteromorphic X-chromosome bivalent, FR1/+, the shorter crossover products were recovered on the average more frequently than the longer reciprocals as predicted by Novitski's (1951) hypothesis of nonrandom disjunction (NRD). The present study stemmed from an unexpected result of these crosses. Evidence for a centromeric effect on NRD was obtained, suggested by a negative correlation between the degree of NRD, c, and the distance between the region of exchange and the centromere as inferred from SET's (single exchange tetrads). Studies on sex chromosome systems other than FR1 confirmed these results. An analogous centromeric effect on preferential segregation had been clearly demonstrated in maize (Kikudome 1958, 1959; Rhoades and Dempsey 1966). However, prior to the present investigation, no such effect of the centromere on NRD in Drosophila had been described, although reanalysis of part of the data of Novitski (1951) and Novitski and Sandler (1956) suggests some evidence of a seriation of increasing c values extending from the most distal region of the chromosome toward the centromere. A suggestion that the effect in Drosophila may be related in some way to the time required for chiasma terminalization, i.e., those terminalizing earlier (distally located crossovers) permitting more random disjunction of the chromatids from the asymmetric dyad and those terminalizing later, progressively less random, is considered and rejected since in general the expected pattern of c values for the various double exchange tetrads (DET's) is inconsistent with that prediction and provides evidence suggesting the possibility of reversals, in part, of c values obtained for SET's.
The present study confirms the findings of Zimmering and Bendbow [28], that there is preferential recovery of the shorter elements of asymmetric dyads following induced exchanges in irradiated T(2;-3)bwv4 males. Deletion studies giving rough estimates of contaminations of phenotypic crossovers by deletions (or point mutations) have now provided more accurate estimates of the degrees of non-randomness (c) in the regions studied. The significance of the V4 studies and their implications on the mechanisms of meiotic drive are discussed.
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Crossing over in the interstitial region of the heterozygous V(4) translocation in Drosophila melanogaster generates asymmetric dyads each consisting of a shorter and a longer chromatid. It was shown previously that in the female the shorter is recovered preferentially (Zimmering 1955); the present work suggests that the same occurs in the male as well. The mechanism in the female is envisioned as involving the non-random inclusion of the shorter chromatid into the functional egg (Novitski 1951); in the male, the two formal possibilities appear to be (1) that some proportion of sperm carrying the longer chromatid derived from an asymmetric dyad undergoes dysfunction, or (2) the longer chromatid is preferentially included into regularly-produced nonfunctional sperm, the nonfunctionality set up at the second division and distinguishing second division daughter cells.
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