Date of Award:
Master of Science (MS)
John R. Simmons
John R. Simmons
D. M. Hammond
Investigations involving the fluorinated pyrimidine, 5-fluorouracil, and its effects on viruses, bacteria, plants and mammals, have brought to light the following facts: FU inhibits the growth of bacteria, plants and mammalian cells and it decreases the ability of certain viruses to produce progeny. In other words, FU is an antimetabolite that inhibits growth and/or reproduction. Two mechanisms have emerged from these studies to define the mode of action of FU. The first mechanism involves the incorporation of the compound into the RNA of the organism thus altering the base sequence and creating a non functional or damaging nucleic acid. The second mechanism concerns the blockage of the methylating enzyme, thymidylate synthetase, which catalyzes the reaction converting dUMP to TMP. When this enzyme is blocked it would, of course, follow that DNA synthesis would be inhibited. FU has not been shown to be incorporated into DNA but 5-trifluoromethyluracil has (Gottschling and Heidelberger, 1963).
No work has been done with FU and its effects on Drosophila but some work has been done with its biological effects on the housefly, Musca domestica (Kilgore and Painter, 1962). In Musca, FU was very toxic when fed in the diet. When 5-FU-2-14C was ingested, it was found that almost all of the compound was passed out in the excreta as waste product. Some 14C, however, was incorporated into the egg, either as FU or one of its metabolic products. An inverse relationship exlsted between the amount of 14C in the egg and hatchability. To account for the lethality it has been proposed (Kilgore, personal communication) that the FU is incorporated into the nucleic acids, specifically RNA, producing a non functional nucleic acid.
In preliminary investigations with FU and its biological effects on Drosophila, it was noted that the compound had a pronounced lethal effect. As was noted earlier, two main possibilities exist to explain this lethal effect in Drosophila and it is the purpose of this investigation to examine those possibilities.
Jenkins, John B. Jr., "A Study of 5-Fluorouracil: Its Effects and Mode of Action in Drosophila melanogaster" (1965). All Graduate Theses and Dissertations. 8256.
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