Biochemical and genetic basis of the response to 5-fluorouracil in Drosophila melanogaster.

Mutant strains sensitive and resistant to the drug 5-flourouracil (FU) have been isolated from the wild-type Pac strain of Drosophila melanogaster. The resistant strain, termed flu, is resistant to at least o.00035%FU (2.7x10(-4)M) in the food media and exhibits cross-resistance to 5-fluorodeoxyuridine (FUdR) but not to 5-fluorouridine (FUR). The sensitive strain termed flus, exhibits over 90% mortality on 0.0008%FU (6x10(-15)M). Genetic analysis indicates that the flu gene is located on the third chromosome, which agrees with results of previous workers. An analysis of the enzyme thymidylate synthetase from the selected sensitive and resistant strains indicates that the resistant strain enzyme possesses an elevated specific activity. Levels 4 times that of the sensitive strain were observed when the enzymes were assayed at 20C. This increase is apparently not due to induction by FU in the food media. It is suggested that the enzyme thymidylate synthetase may be involved in the resistance process.