Liver Genomic Responses to Ciguatoxin (P-CTX-1). Mus musculus

Ciguatoxins (CTX) are polyether neurotoxins responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post exposure 2.4% of features on a 44K whole genome array were differentially expressed (p ≤ 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Early gene expression was likely influenced prominently by an acute 4 °C decline in core body temperature by 1 h, which resolved by 8 h following exposure. Cytochrome P450s were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial down-regulation at 1 h but were quickly and strongly up-regulated at 4 and 24 h post exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice. Keywords: biotoxin, time course Overall design: Individual C57/BL6 mice (n=3) exposed to 0.26 ng/g P-CTX-1 ip for 1, 4, or 24 h were compared to pooled time-matched controls (n=3). The triplicate arrays at each time point included a dye swap.