Arsenic Reduces Gene Expression Response to Changing Salinity in Killifish

Toxicogenomic
approaches can detect and classify adverse interactions
between environmental toxicants and other environmental stressors
but require more complex experimental designs and analytical approaches.
Here we use novel toxicogenomic techniques to analyze the effect of
arsenic exposure in wild killifish populations acclimating to changing
salinity. Fish from three populations were acclimated to full strength
seawater and transferred to fresh water for 1 or 24 h. Linear models
of gene expression in gill tissue identified 31 genes that responded
to osmotic shock at 1 h and 178 genes that responded at 24 h. Arsenic
exposure (100 μg/L) diminished the responses (reaction norms)
of these genes by 22% at 1 h (p = 1.0 × 10–6) and by 10% at 24 h (p = 3.0 ×
10–10). Arsenic also significantly reduced gene
coregulation in gene regulatory networks (p = 0.002,
paired Levene’s test), and interactions between arsenic and
salinity acclimation were uniformly antagonistic at the biological
pathway level (p < 0.05, binomial test). Arsenic’s
systematic interference with gene expression reaction norms was validated
in a mouse multistressor experiment, demonstrating the ability of
these toxicogenomic approaches to identify biologically relevant adverse
interactions between environmental toxicants and other environmental
stressors.