title: Integrative toxicopathological evaluation of aflatoxin B₁ exposure in F344 rats.
abstract: In this study, male F344 rats were orally exposed to a single dose of aflatoxin B₁ (AFB₁) at 0, 50, 250, or 1,000 µg/kg body weight (BW) or repeated dose of 0, 5, 10, 25, or 75 µg/kg BW for up to 5 weeks. Biochemical and histological changes were assessed together with the formation of AFB1-lysine adduct (AFB-Lys) and liver foci positive for placental form glutathione S transferase (GST-P⁺). In single-dose protocol, serum aspartate transaminase (AST), alanine transaminase (ALT), and alkaline phosphatase (ALP) showed dose-related elevation, with maximal changes observed (>100-fold) at day 3 after treatment. Animals that received 250 µg/kg AFB₁ showed concurrent bile duct proliferation, necrosis, and GST-P⁺ hepatocytes at 3 day, followed by liver GST-P⁺ foci appearance at 1 week. In repeated-dose protocol, bile duct proliferation and liver GST-P⁺ foci co-occurred after 3-week exposure to 75 µg/kg AFB₁, followed by proliferation foci formation after 4 week and dramatic ALT, AST, and CK elevations after 5 weeks. Liver GST-P⁺ foci were induced temporally and in a dose-related manner. Serum AFB-Lys increased temporally at low doses (5-25 µg/kg), and reached the maximum after 2-week exposure at 75 µg/kg. This integrative study demonstrated that liver GST-P⁺ cells and foci are sensitive biomarkers for AFB₁ toxic effect and correlated with bile duct proliferation and biochemical alterations in F344 rats.
authors: 1Department of Environmental Health Science, University of Georgia, Athens, Georgia, USA.
authors: Guoqing
authors: G
authors: Qian
authors: Franklin
authors: F
authors: Wang
authors: Lili
authors: L
authors: Tang
authors: Michael E
authors: ME
authors: Massey
authors: Nicole J
authors: NJ
authors: Mitchell
authors: Jianjia
authors: J
authors: Su
authors: Jonathan H
authors: JH
authors: Williams
authors: Timothy D
authors: TD
authors: Phillips
authors: Jia-Sheng
authors: JS
authors: Wang
mesh_terms: D016604:Aflatoxin B1 / Q000097:blood / Q000378:metabolism / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D001652:Bile Ducts / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D005982:Glutathione Transferase / Q000378:metabolism; D006651:Histocytochemistry; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008239:Lysine / Q000097:blood / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D011916:Rats, Inbred F344; D018675:Toxicity Tests / Q000379:methods*
chemical_list: C066451:aflatoxin B1-lysine adduct; D016604:Aflatoxin B1; D005982:Glutathione Transferase; D008239:Lysine
keywords: aflatoxin B1; aflatoxin B1-lysine; biochemistry.; histology; placental form glutathione S transferase