Worm Breeder's Gazette 13(1): 88 (October 1, 1993)
These abstracts should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.
Fluoroacetic acid which inhibits aconitase, an enzyme in both the Krebs and glyoxylate cycles, was discovered to be a potent and specific inhibitor of reproduction in a toxicity test using the nematode Caenorhabditis elegans. Fluoroacetic acid reduced reproduction in the second generation by 50% at concentrations 3000 times lower than the LC(50) of 76 mM. Four concentrations (1.7, 4.2,8.5, and 17 mM) of fluoroacetic acid were tested thoroughly. At the two lower concentrations the survival rates were unaffected, and first generation reproduction was greatly reduced but not completely eliminated. Survival was reduced at the higher concentrations. To determine whether fluoroacetic acid inhibited reproduction because it interfered with both the Krebs cycle and the glyoxylate cycle, malonic acid which inhibits the Krebs cycle and itaconic acid which inhibits the glyoxylate cycle were tested individually and in combination against C. elegans. If the potent reproduction effect of fluoroacetic acid relative to lethality is caused by inhibiting both the Krebs and glyoxylate cycles, the combination of malonic acid and itaconic acid would be expected to produce results qualitatively similar to those obtained with fluoroacetic acid. For the mixture, a large ratio of the LC(50) to EC(50) for reproduction would indicate synergy. Concentration-response curves for the survival assay and the reproduction assay were developed for each test compound and combination of compounds. The probit method was used to calculate the LC(50) and EC(50) for reproduction. The ratio of the LC(50) to EC(50) was calculated for each and is presented in the Table. The combination did not specifically inhibit reproduction, suggesting another mode of action for fluoroacetic acid, possibly one that is specific to reproduction and possibly one which affects aconitase.