Fig. 3: Host long-chain fatty acid synthesis modulates tamoxifen toxicity.

a Screening a metabolic gene RNAi library identified three genes (dhs-19, elo-3, and elo-5) that, when knocked down, increase TAM toxicity. Animals were fed E. coli HT115 expressing double-stranded RNA as indicated. Control indicates E. coli containing vector control plasmid (pL4440). Bright-field images were taken at 2x magnification after a 48 h exposure to tamoxifen. Scale bars: 1 mm. Representative results of one from three independent experiments. b Tamoxifen dose-response curves comparing Δdhs-19 mutant animals to wild-type animals. Data were represented as mean ± SEM of three independent biological replicates. Statistical significance was assessed by performing a two-way Anova without a post hoc test, on Graphpad Prism (v9). **p value: 0.0008. c C. elegans fatty acid biosynthesis pathway. Gene names are colored by enzymatic function: FA elongation in blue, FA desaturation in pink, and acyl-CoA synthesis in purple. d Cartoon illustrating calculation of differential area under the curve (ΔAUC) used in panels e and f. AUCs were calculated using average DRCs. Statistical significance was assessed by performing two-way Anovas using Graphpad Prism (v9) on original DRCs and is reported in Supplementary Table 2. See also Supplementary Fig. 5. e, f Bar graph showing ΔAUC values obtained from average full DRCs for animals exposed to RNAi of indicated genes. Source data are provided as a Source Data file.