Effects of dietary aflatoxin on the hepatic expression of apoptosis genes in growing barrows1

• Published in: Journal of animal science Vol. 89; no. 4; pp. 916 - 925
• Main Authors: Rustemeyer, S. M., Lamberson, W. R., Ledoux, D. R., Wells, K., Austin, K. J., Cammack, K. M.
• Format: Journal Article
• Language: English
• Published: Champaign Oxford University Press 01.04.2011
• Subjects: Animal sciences; Apoptosis; Gene expression; Hogs; Ribonucleic acid; RNA; Toxins
• ISSN: 0021-8812; 1525-3163
• DOI: 10.2527/jas.2010-3473

The most common and toxic form of aflatoxin, aflatoxin B^sub 1^ (AFB^sub 1^), is produced by molds growing on crops. Use of moldy corn can result in high concentrations of AFB^sub 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^sub 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^sub 1^, 250 µg/kg of AFB^sub 1^, or 500 µg/kg of AFB^sub 1^ for 7, 28, or 70 d. Because performance was most affected in animals administered AFB^sub 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^sub 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^sub 1^-contaminated diet to growing barrows alters hepatic gene expression, and in particular apoptosis genes. [PUBLICATION ABSTRACT]