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Title: Studies on spontaneous and induced mutation
Author: Auerbach
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1947
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Mutation is one of the basic processes of life. It is the ultimate source of hereditary variability and as such an essential prerequisite for evolution. Yet in spite of the great achievements of radiation genetics in the last 20 years, the nature of the mutation process is still unknown. The work presented here is an attempt to approach this problem through a study of chemical substances affecting mutation rates. It includes one paper on spontaneous mutation which grew out of incidental observations made in the course of an experiment with chemical treatment. Drosophila melanogaster was used throughout as test animal. The first substances to b'e tested for mutagenic capacity were carcinogenic hydrocarbons. The use of these substances was suggested through the theory, supported by a number of scientists, that cancer is due to mutation in somatic cells. The results of mutation tests failed to give evidence in favour of this theory, and work along these lines was dropped for the time being (1). In the course of this work, a sex difference had been noted, mutation rates being higher in the X- chromosome of males than of females, independent of treatment. In a number of large -scale tests with untreated flies this difference in the incidence of spontaneous mutations in the sexes could be substantiated (2) . In 1940, Prof. A. Clark and Dr J.M. Robson from the Department of Pharmacology drew my attention to the pharmacological similarities between mustard gas and X-rays. We considered the possibility that mustard gas, like X-rays, might exercise an action on the chromosomes. In collaboration with Dr Robson, experiments were started to test this hypothesis. The results of these experiments, being subject to a security -ban, could not be published during the war. They were submitted to the Ministry of Supply in two reports (W 3979 and W 11331) which were handed in on the 14th of March and the 4th of June 1942. Permission for publication has only recently been obtained. For this reaeon most of the publications concerning this work are still in press, apart from a few preliminary notes (3,4,5). The papers which are in press are here submitted as proof or in typescript. Our data show that mustard as is an extremely efficient muta` :en, comparable in degree of mutagenic activity to high-energy radiation. Like X-rays, it causes sterility through interference with gametogenesis. It causes dominant lethality, chromosome re-arrangements, visible and recessive lethal mutations (6). Most experiments were carried out with doses which produced between 6 and 13. of sex-linked lethals, but in one experiment as many as 24 were obtained. Visible mutations were mainly of the types which had occurred previously after irradiation or spontaneously, and no specific action of the gas on particular loci was observed. The frequency of translocations in several experiments fell short of what would have been expected from a dose of X -rays producing the same frequency of recessive lethals. A number of substances which either in their pharmacological action or their chemical structure are related to mustard as were next tested for possible action on chromosomes and genes. Several of them, all belonging to the class of the so- called nitrogen -or sulphur -mustards, were shown to be as potent as mustard `as. In addition, allyl inothiocyauia.te behaved as a weak, but definite auta-en. Two tested substances, chloaracetone and d.ichloracetore, possibly have a slight mutagenic action. Lewisite, picric acid and o.smic acid gave negative results. These data were submitted to the Yinistry,of ^up ^ly on Dec. 33rd 1943 (Report Y 10171). A full report is in press (7). In addition to their Pharmacological interest, these results open up a new means of analyzing the process of mutation. Work along these lines was carried out, without the cooperation of Dr Robson. Attempts were IA i_-dur :c, somatic mutations through treatment of Drosophila Embryos with mustard Gigs, ri Üreat number of apparent somatic mutations were obtained, but subsecuent analysis revealed that most or all of them. were in reality somatic crossovers (8). These tests therefore show a very strong influence of mustard as on somatic. crossing over, At the same time they suggest, as has indeed been urged before by Stern, that also after X- radiation. of embryos the apparent somatic mutations may in fact be the results of somatic crossing-over, Partioular interest attaches to the differences between the mutagenic action. Of radiation on the one hand, chemical substances on the other. One of these differences consists in the strikingly high percentage of mosaic individuals among the progeny of chemically treated males. Analysis of this phenomenon led to the assumption that mustard gas, unlike X-rays, may exercise a delayed action on the chromosomes (9). An extension of this work to a study of mosaics for sex-linked lethals lent further support to this hypothesis (10).
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available