Mebendazole inhibits the growth, reproductive capacity, and motility of Caenorhabditis elegans. Maximum reduction of length (50%) and volume (80%) was observed at 6.25 μg/mL mebendazole. At this concentration vulva formation was delayed by 18 h and egg production was reduced from 8 eggs/worm per hour to less than 1. The critical period for the effect of mebendazole on length was from 40 to 50 h after hatching. The drug did not affect the viability of eggs, larvae, or adults. L1 and L2 larvae were motile in the presence of mebendazole (6.25 μg/mL); paralysis became apparent during the L3 and was complete in L4 and adult stages. Paralysed worms coiled into a ring and moved feebly and spasmodically. The first two moults occurred at the same time in control and treated worms, the L3/L4 and L4/adult moults were delayed by less than 1 h in the presence of the drug. Evidence is presented that these observed effects are caused by mebendazole and were not the consequence of partial starvation resulting from paralysis.

1989. The genetics, ultrastructure, and tubulin polypeptides of mebendazole-resistant mutants of Caenorhabditis elegans. Can. J. Zool. 67: 2422 -2431. Mebendazole-resistant mutants of Caenorhabditis elegans were isolated following mutagenesis of the wild-type strain, N2, with ethylmethane sulphonate. The mutants define a single autosomal gene and are allelic to ben-1. They grow, move, and reproduce normally in the presence of mebendazole and are cross-resistant to albendazole, cambendazole, fenbendazole, methylbenzimidazole carbamate, and thiabendazole. Accumulations of membrane-bound, electron-dense material associated with the nervous tissue and associated cells are seen in electron micrographs of L3, LA, and adult stages of N2 grown in the presence of mebendazole, but are not found in the mutants. The electron-dense material appears to be associated with the accessory cells of the neuropil rather than with the neurons. The tubulins from wild type, N2, and the mutants were characterised by two-dimensional electrophoresis followed by silver staining and Western blotting with monoclonal antibodies to a -and P-tubulin. A single isotype of a-tubulin is apparent in both N2 and the mutants. One major and three minor P-tubulin isotypes, bt-1 to bt-3, can be discerned in N2; the minor isotype bt-2 is absent in all the mutants. These findings suggest that the isotype bt-2 is the primary site of action of benzimidazole-based drugs in C. elegans.

1986. The effects of amidantel (BAY d 88 15) and its deacylated derivative (BAY d 9216) on wild-type and resistant mutants of Caenorhabditis elegans. Can. J . Zool. 64: 1310-1316. The anthelmintic drugs amidantel (BAY d 88 15) and its deacylated derivative (BAY d 9216) inhibited the growth of wild-type (N2) Caenorhabditis elegans but had little effect on development or reproductive capacity. Inhibition of growth correlated well with drug-induced paralysis, both becoming maximal at around 1 .O mM concentration of either drug. Egg laying was delayed by about 24 h and the rate of laying was only about 60-70% of the controls. However, the period during which eggs were laid was extended by a similar amount and the total number of eggs laid was the same for controls and drug-treated worms. Five drug-resistant mutants (TI 14, T22, T26, T21 6, and T226) were isolated following ethylmethanesulphonate mutagenesis. All were shorter than N2 at 96 h on drug-free medium; their growth was not further impaired by either of the anthelmintic drugs. All except T I 14 exhibited a normal pattern of sexual maturation. Cultures of T I 14 at 96 h contained many immature worms. This mutant also exhibited the most impaired motility, being severely uncoordinated in liquid suspension. The other mutants could swim normally but were noticeably slower than N2. Genetic analysis indicated that each mutant was the result of a single genetic lesion, that the mutants were recessive, and that there were two genes for amidantel resistance (adtl and adt2). In vitro studies on representatives of each class (T114 and T22) indicated a defect in the acetylcholine receptor. T22 mutants showed a moderate decrease in sensitivity towards typical cholinergic agonists as well as the anthelmintic drugs, while T I 14 mutants were apparently devoid of functional pharmacological acetylcholine receptors. WOODS, R. A., K. M. B. MALONE, C. A. ALBUQUERQUE et G. TOMI~INSON. 1986. The effects of amidantel (BAY d 88 15) and its deacylated derivative (BAY d 9216) on wild-type and resistant mutants of Caenorhabditis elegans. Can. J . Zool. 64: 1310-1316. L'amidantel (BAY d 88 15), une substance anti-helminthes, ou son derive desacetyle (BAY d 9216) inhibent la croissance des Caenorhabditis elegans de type sauvage (N2), mais n'ont que peu d'effet sur le d~v e l o~~e m e n t ou sur la capacite reproductrice des vers. I1 y a une forte correlation entre l'inhibitation de la croissance et la paralysie qu'entralnent les substances et ces deux facteurs atteignent leur sommet lorsque la concentration de la substance atteint 1 ,O mM. La ponte est retardee d'environ 24 h et le taux de ponte n'atteint que 60-70% de la valeur enregistree chez les tCmoins. Cependant, la ponte dure plus longtemps chez les vers traites et le nombre total d'oeufs pondus est semblable a celui qui prevaut chez les temoins. Cinq mutants resistants aux produits (TI 14, T22, T26, T216 et T226) ont kt6 isolks apres une mutagenese causee par de l'ethyl-methane-sulfonate. Tous les mutants sont plus courts que N2 ...