title: Effects of chronic deoxynivalenol exposure on p53 heterozygous and p53 homozygous mice.
abstract: 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.
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada. Electronic address: Genevieve.Bondy@canada.ca.
authors.forename: G S
authors.initials: GS
authors.lastname: Bondy
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Coady
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Curran
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Caldwell
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Armstrong
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: S A
authors.initials: SA
authors.lastname: Aziz
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Nunnikhoven
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: A M
authors.initials: AM
authors.lastname: Gannon
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Liston
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Shenton
authors.affiliation: Regulatory Toxicology Research Division, Bureau of Chemical Safety, Food Directorate, Health Products and Food Branch, Health Canada, Ottawa, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Mehta
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects*; D005434:Flow Cytometry; D006579:Heterozygote; D006720:Homozygote; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D007668:Kidney / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014255:Trichothecenes / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
chemical_list: D007136:Immunoglobulins; D012333:RNA, Messenger; D014255:Trichothecenes; D016159:Tumor Suppressor Protein p53; C007262:deoxynivalenol
keywords: Cancer; Chronic; Deoxynivalenol; Diet; Inflammation; Mouse; p53