Ultrastructural Effects of 5-Bromodeoxyuridine and 5-Fluorouracil in Drosophila¹

The frequency of perichromatin granules (PG's) has been used as a quantitative phenotype to assess intracellular effects of halogenated pyrimidine analogs on Drosophila. Administration of 5-fluorouracil (FU) p.o. to third-instar larvae decreased the frequency of intranuclear PG's in the fat body cells, while larvae treated with FU + 5-bromodeoxyuridine (BUdR) had the same PG frequency as did control larvae on H₂O or the regular Drosophila diet. PG frequency in larvae receiving only BUdR was decreased, but to a smaller extent than in larvae given FU. Unusual configurations of membranous elements in association with PG (MPG) were noted in the cytoplasm of some of the cells of the treated larvae. The incidence of MPG was highest in larvae fed FU + BUdR and similar in larvae given BUdR or H₂O; no MPG were found in the sample of larvae given FU. This feature in the cells of the treated groups of larvae may be an exaggeration of a process normally occurring in the cytoplasm, since several instances of PG's attached to short membranes were found in the fat body cells of larvae feeding on the normal diet. There is no apparent correlation between the incidence of MPG formation in the larval fat body cells and the incidence of neoplasia and other growth modifications previously described in the imaginal structures of Drosophila following treatment with FU + BUdR.

During the third larval instar, the density of PG in the nuclei of normal Oregon-R fat body cells increases linearly, whereas PG density in vermilion mutant fat body cells remains low throughout this period of development. The frequency of PG detectable as free units in the nuclear space may also be modified by experimental manipulations such as incubation of fat body cells in Ringer solution and treatment of isolated nuclei with deoxycholate.