Date of Award

1993

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Biological Sciences

First Advisor

William R. Lee

Abstract

Tritium beta radiation (tritium) was used to induce mutations at the alcohol dehydrogenase (Adh) locus in male Drosophila melanogaster post-meiotic germ cells. All 23 mutations recovered were deletions greater than one kilobase in size (multikilobase deletions) as determined by genetic complementation analysis. A statistical difference was observed between the frequency of multikilobase deletions (23/23 or 1.0) induced by tritium and the frequency of multikilobase deletions (19/27 or 0.7) induced by 100-kVp X-radiation (X-rays). The relative frequency of multikilobase deletions induced by tritium with respect to that induced by X-rays was 1.4. This value was compared to the relative biological effectiveness (RBE = 1.4) of these 2 radiation sources, determined from the ratio of the regression coefficients of the respective sex-linked recessive lethal (SLRL) dose-response data. A relationship may exist between the relative frequency of multikilobase deletions induced at the Adh locus and the RBE determined from the SLRL dose-response data. In addition, a genetic map of the multikilobase deletion break-points induced by tritium and by three monofunctional alkylating agents, 1-ethyl-1-nitrosourea, 1-methyl-1-nitrosourea and ethyl methanesulfonate, is presented. Previous in vitro research suggests that 2-chloroethyl methanesulfonate (Cl-EMS) will produce the same DNA adduct as 1,2-dichloroethane or 1,2-dibromoethane. D. melanogaster gonial cells were treated with Cl-EMS, and the sex-linked recessive lethal (SLRL) and alcohol dehydrogenase (Adh) induced mutation frequencies were determined. The results of these studies were the following: First, mutation frequencies 200 times the spontaneous mutation frequency were induced with Cl-EMS. Second, lethal mutations on the X-chromosome were selected against in the hemizygous male. Third, the induced Adh mutation frequency was higher in the male than in the female. Fourth, all of the 83 Adh null mutations recovered were intragenic mutations as determined by complementation analysis. Fifth, treatment of gonial cells resulted in mutations of common origin, verified by DNA sequence analysis. Sixth, all 36 mutations of independent origin were GC to AT transitions. This study was supported by NIEHS PO1-EEO3447 and DE-FG05-86ER60393.

Pages

112

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