Effects of dietary aflatoxin on the hepatic expression of apoptosis genes in growing barrows.

The most common and toxic form of aflatoxin, aflatoxin B(1) (AFB(1)), is produced by molds growing on crops. Use of moldy corn can result in high concentrations of AFB(1) in swine diets, which could potentially lead to an increased incidence of aflatoxicosis, a disease associated with decreased health and performance through reduced feed intake, reduced BW gain, and impaired liver function. The objective of this study was to determine the effects of AFB(1) on the hepatic gene expression of growing barrows. Ninety Duroc × Yorkshire crossbred barrows (age = 35 ± 5 d; initial BW = 14.2 ± 3.0 kg) were allocated to 9 pens with 10 pigs per pen, and randomly assigned in a 3 × 3 factorial arrangements of treatments to receive diets containing 0 µg/kg of AFB(1), 250 µg/kg of AFB(1), or 500 µg/kg of AFB(1) for 7, 28, or 70 d. Because performance was most affected in animals administered AFB(1) for an extended period, liver samples from d 70 animals were used for RNA-sequencing analysis. Of 82,744 sequences probed, 179 had transcripts that were highly correlated (r ≥ |0.8|; P < 0.0001) with treatment. Of the 179 significant transcripts, 46 sequences were negatively and 133 sequences positively related to treatment. Forty-three unique functional groups were identified. Genes within the apoptosis regulation functional group were selected for 1) confirmation of d 70 gene expression differences using real-time reverse-transcription (RT)-PCR (n = 4 genes), and 2) investigation of d 7 expression to identify early responses to AFB(1) (n = 15 genes) using real-time RT-PCR. Expression of the 4 apoptosis genes selected for confirmation, cyclin-dependent kinase inhibitor 1A, zinc finger matrin type 3, kininogen 1, and pim-1 oncogene, was confirmed with real-time RT-PCR. Of the 15 genes tested in d 7 liver samples, 4 were differentially expressed: cyclin-dependent kinase inhibitor 1A; zinc finger matrin type 3; tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, zeta polypeptide; and apoptosis enhancing nuclease. Results from this study demonstrate that administration of an AFB(1)-contaminated diet to growing barrows alters hepatic gene expression, and in particular apoptosis genes.