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Biomedical subjects

F H Sobels

Publications and source records attributed to F H Sobels.

At least 37 records · Page 2Linked to original sources
PubMed1983

The effect of two chemical mutagens ENU and MMS on MR-mediated reversion of an insertion-sequence mutation in Drosophila melanogaster.

The effects of two mutagens ENU and MMS characterized by different alkylation patterns have been studied on the reversion of an MR-induced singed mutation to wild-type. Reversion of this unstable singed mutation under the influence of MR is assumed to represent the removal or transposition of an insertion element. Since MR acts primarily in spermatogonia, the mutagens were fed to 1st instar larvae. Recessive lethal tests were carried out simultaneously to calibrate for the mutagenic effectiveness of the chemicals. For both powerful mutagens, it was observed that the frequency of reversion remained far below of what would have been expected on the basis of the mutagenic effectiveness, as registered in the lethal tests. Thus 1 mM ENU, 5 mM and 10 mM MMS did not affect the reversion frequency at all, and with 3 mM ENU only a doubling of the reversion frequency was observed, despite a 5-fold increase in the lethal frequency. The threshold at 1 mM EMU and the low effectiveness of 3 mM on the reversion process are taken as an indication that ENU affected the transposition process in an indirect manner, rather than the excision events themselves. The data obtained with Drosophila are consistent with the microbial observations in that mutation involving removal or transposition of an insertion element is not affected by mutagenic treatments. This finding may have consequences for the evaluation of induced genetic damage on the basis of the spontaneous load of genetic detriment in man. An incidental observation was that non-MR Cy larvae exhibited greater sensitivity to the induction of recessive lethals by MMS than MR-individuals.

Animals↗
PubMed1983

Evaluation of the mutagenic potential of the hair dye N-methyl-amino-2-nitro-4-N',N'-bis-(2-hydroxyethyl)-aminobenzene in a battery consisting of Drosophila and mammalian cytogenetic assays.

The compound N-methyl-amino-2-nitro-4-N', N'-bis(2-hydroxyethyl)-aminobenzene was tested for mutagenic activity in the sex-linked recessive lethal test with Drosophila melanogaster, the induction of chromosomal aberrations and sister-chromatid exchanges (SCEs) with Chinese hamster ovary (CHO) cells in vitro, and the micronucleus test with mouse bone-marrow cells in vivo. Consistently negative results were obtained with the 3 tests. The SCE tests gave positive results with prolonged treatments. It is concluded that reliable decisions about mutagenic activity cannot be based on the induction, in vitro, of SCEs alone.

Animals↗
PubMed1981

Modification of MR mutator activity in repair-deficient strains of Drosophila melanogaster.

In drosophila, MR (male recombination) second chromosomes are known to act as mutators and recombination-inducers in males. One explanation of MR- induced effects is that MR causes breaks at specific sites where, subsequently, insertion sequences become integrated. To examine the extent to which excision and incorporation of DNA sequences by MR is affected by enzymatic pathways involved in DNA repair, the following experiments were carried out. MR-chromosomes were introduced into males deficient for excision (mei-9a) or post-replication repair (mei-41D5) or into males carrying both repair-deficient mutations. MR activity was recorded by the occurrence of visible mutations at the sn (singed) and ras (raspberry) loci. The spontaneous mutation frequency for sn is 0.2 . 10-5 (1/490 000) and for ras, 0.4 . 10-5 (2/490 000). When MR is introduced into repair-proficient males the frequency of sn mutations is 51 . 10-5 (16/30 795) and of ras mutations is 19. 10-5 (6/30 795). In MR males deficient for both excision and post-replication repair (mei-9a mei-41D5) mutator activity is significantly enhanced; the frequency of sn mutations amounts to 225 . 10-5 (174/77 219) and of ras mutations to 135 . 10-5 (104/77 219). mei-9a or mei-41D5 alone also leads to an enhancement of the mutation frequencies, but this effect is of borderline significance.

Animals↗
PubMed1981

Influence of the MR (mutator) factor on X-ray-induced genetic damage.

The genetical effects induced by MR, in the progeny of outcrossed MR-males, include very high frequencies of visible and lethal mutations and chromosome aberrations. The hypothesis is that MR causes breaks at specific sites in the DNA where, subsequently, insertion sequences become integrated. To examine whether there exists an interaction between breaks and radiation induced lesions, MRh12/Cy males were crossed to Berlin K females and the male progeny from this cross carrying the MR or Cy chromosome were irradiated. The frequencies of X-linked recessive lethals and II-III translocations were determined. Non-irradiated MR and non-MR (Cy) male progeny were used in concurrent controls. The results show that the frequencies of II-III translocations in the MR-containing males is not significantly higher than in the controls. However, with regard to the production of recessive lethal mutations a clear synergism between MRh12 and X-irradiation was observed.

Animals↗
PubMed1981

Neutrons and X-rays, comparative studies with Drosophila melanogaster. 2. Sex-chromosome loss and partial loss, evidence for the induction of chromatid aberrations in spermatozoa.

Losses and duplications of BSY y+-chromosome markers were induced by irradiation of spermatozoa with either 0.5-MeV neutrons or 100-kV X-rays. These 2 types of radiation are known to induce significantly different ratios of double:single strand breaks in DNA. Exceptional progeny were grouped into 3 categories; no Y marker, one Y marker, and Y marker duplications + mosaics. The last combination consisted of exceptions derived from only chromatid-type rearrangements. All other classes of exceptions may be derived from either chromatid- or chromosome-type rearrangements. Doses of 15 Gy neutrons and 27 Gy X-rays induced identical frequencies of exceptional progeny, giving an RBE of 1.8. The ratios of the 3 classes of exceptions were similar for both types of radiation. This observation can be interpreted as indicating that, under the conditions used here, chromosome and chromatid rearrangements are not derived directly from double and single DNA strand breaks, respectively.

Animals↗
PubMed1979

The effect of exposure fractionation on the yield of nondisjunctional segregation involving compound X and free 4-chromosomes in Drosophila.

This paper describes the effect of fractionation of an exposure of 2000-R X-rays into two 1000-R exposures separated by a 3-h interval on the frequency of various segregation products following chromatoid interchange between a compound X and the 4th chromosome. It was observed that fractionation leads to a decrease of all exceptional progeny, the result being significant at the 0.05-probability level for both classes of detachments; i.e., with or without a 4th chromosome. The finding that the same effect of fractionation was observed for numerical aberration (non-disjunction) and detachment supports the idea that these reflect different consequences of the same primary effect, radiation-induced rearrangement. Furthermore, alternative recoveries were observed to occur at equal frequencies. Following C(1)-4 interchange, the univalent 4 does not segregate at random, but assorts apart from its homologue 1.5 as frequently as it moves to the same pole.

Animals↗
PubMed1979

Is there a proportionality between the spontaneous and the X-ray-induction rates of mutations? Experiments with mutations at 13 X-chromosome loci in Drosophila melanogaster.

The X-ray induction of recessive visible specific locus mutations at 14 X-chromsome loci was studied in Drosophila melanogaster using the "Maxy" technique. The X-ray exposure was 3000 R to 5-day-old males and the sampling of germ cells was restricted to mature spermatozoa. Presumptive mutant females recovered in the F1 generation were tested for transmission, allelism, fertility and viability in males. A total of 128 mutations (115 completes and 13 mosaics including those that were male viable as well as male-lethal) recovered among 38 898 female progeny were found to be transmitted. On the basis of the above frequency, the average mutation rate can be estimated as 7.8 X 10(-8)/locus/R; for mutations that were viable and fertile in males, the rate is 3.0 X 10(-5)/locus/R (49 mutations among 38 898 progeny). The frequency of mutations at the different loci encompassed a wide range: while no mutations were recovered at the raspberry and carnation loci, at others, the numbers ranged from 1 at echinus to 31 at garnet; in addition, the proportion of mutations that was male-viable was also different, depending on the locus. Schalet's extensive data on spontaneous mutations at 13 (of the 14 loci employed in the present study) loci permit an estimate of the spontaneous rate which is 6.1 X 10(-6)/locus (a total of39 mutations among 490 000 progeny); for mutations that were viable and fertile in males, the rate is 3.0 X 10(-6)/locus (19 mutations among 490 000 progeny). The mutability of the different loci varied over a 9-fold range. When the different loci are ranked depending on their relative mutability (for spontaneous and induced mutations) it is found that in general, loci that mutate spontaneously relatively more frequently are also those at which more mutations have been recovered in the radiation experiments and likewise, those that are less mutable spontaneously are also those that mutate less after irradiation. Since the data are limited, it is concluded that the above finding is not inconsistent with the assumption of proportionality between spontaneous and induction rates of mutations. On the basis of the above results, a doubling dose of 100 R can be calculated for the X-ray induction of specific-locus mutations in Drosophila spermatozoa.

Animals↗