Effects of chronic deoxynivalenol exposure on p53 heterozygous and p53 homozygous mice

• Published in: Food and chemical toxicology 2016-10, Vol.96, p.24-34
• Main Authors: Bondy, G.S., Coady, L., Curran, I., Caldwell, D., Armstrong, C., Aziz, S.A., Nunnikhoven, A., Gannon, A.M., Liston, V., Shenton, J., Mehta, R.
• Format: Article
• Language: English
• Subjects: Animals; body weight; Body Weight - drug effects; Cancer; Cell Proliferation - drug effects; Chronic; chronic exposure; Deoxynivalenol; Diet; dose response; Dose-Response Relationship, Drug; Eating - drug effects; Flow Cytometry; food crops; Fusarium; gene expression; genes; genetically modified organisms; heterozygosity; Heterozygote; homozygosity; Homozygote; Immunoglobulins - genetics; Immunoglobulins - metabolism; Inflammation; Inflammation - chemically induced; Inflammation - metabolism; Inflammation - pathology; Kidney - metabolism; Kidney - pathology; Liver - metabolism; Liver - pathology; long term effects; Male; males; Mice; Mice, Knockout; Mouse; neoplasms; p53; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; secondary metabolites; toxicity; toxicology; Trichothecenes - toxicity; Tumor Suppressor Protein p53 - physiology
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2016.07.018

Deoxynivalenol (DON) is a secondary metabolite associated with Fusarium species pathogenic to important food crops. A two-year feeding study reported that DON was non-carcinogenic in B6C3F1 mice. The present study was conducted to further characterize the chronic effects of DON by exposing cancer-prone transgenic p53 heterozygous (p53+/−) male mice and p53 homozygous (p53+/+) male mice to 0, 1, 5, or 10 mg DON/kg in diet for 26 weeks. Gross and microscopic organ-specific neoplastic and non-neoplastic changes and expression profiles of key hepatic and renal genes were assessed. Few toxicologic differences between p53+/+ and p53+/− mice were observed, and no tumours were observed due to DON. The results indicated that DON was non-carcinogenic and that reduced expression of the p53 gene did not play a key role in responses to DON toxicity. The lack of inflammatory and proliferative lesions in mice may be attributed to the anorectic effects of DON, which resulted in dose-dependent reductions in body weight in p53+/+ and p53+/− mice. Hepatic and renal gene expression analyses confirmed that chronic exposure to DON was noninflammatory. The effects of 26-week DON exposure on p53+/+ and p53+/−mice were consistent with those previously seen in B6C3F1 mice exposed to DON for two years. •Deoxynivalenol did not produce tumours in cancer-prone p53+/− mice.•Deoxynivalenol caused feed refusal and reduced body weight gain in mice.•Deoxynivalenol induced gene expression changes indicative of anti-inflammatory and anti-proliferative responses in mice.