Reduction of aflatoxin B1 adduct biomarkers by oltipraz in the tree shrew (Tupaia belangeri chinensis)

Yuan Li, Jian Jia Su, Liu Liang Qin, Patricia A. Egner, Jia Sheng Wang, John D. Groopman, Thomas W. Kensler, Bill D. Roebuck

Research output: Contribution to journalArticlepeer-review

Abstract

The risk of liver cancer is greatest in people both infected with hepatitis B virus (HBV) and highly exposed to aflatoxin B1 (AFB1). The tree shrew (Tupaia belangeri chinensis) is a unique species that can be infected with human HBV, is susceptible to AFB1-induced liver cancer, and shows a synergistic interaction between HBV and AFB1 for liver cancer. In this regard, the tree shrew may be useful for evaluating experimental chemoprevention strategies relevant to high-risk human populations as it mirrors the human epidemiology of liver cancer. To begin developing the model for chemoprevention study, two groups of tree shrews were fed 400 μg AFB1/kg b.wt. in milk daily for 4 weeks. One week prior to AFB1 administration, one group also received oltipraz (0.5 mmol/kg, p.o.) daily for 5 weeks. At weekly intervals, 1 ml of blood and a 24-h urine sample were obtained from each animal. Aflatoxin-albumin adducts in serum were determined by a radioimmunological assay and aflatoxin-N7-guanine adducts in urine were measured by HPLC. Aflatoxin-albumin adducts increased rapidly in 2 weeks to plateau at 20 pmol/mg protein, and they diminished after cessation of AFB1 exposure. Oltipraz significantly attenuated the overall burden of aflatoxin-albumin adducts throughout the exposure period with a median reduction of 80%. In a single cross-sectional analysis at the end of AFB1 dosing, oltipraz treatment decreased urinary aflatoxin-N7-guanine by 93%. Collectively, these results indicate that oltipraz reduces AFB1 risk biomarkers in the tree shrew in a manner similar to that observed in rodents and humans, and establishes a rationale to evaluate cancer chemoprevention by oltipraz in human HBV-infected, AFB1 exposed tree shrews. Copyright (C) 2000 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)79-83
Number of pages5
JournalCancer Letters
Volume154
Issue number1
DOIs
StatePublished - Jun 1 2000

Keywords

  • Aflatoxin B
  • Biomarker
  • Hepatitis B virus
  • Hepatocellular carcinoma
  • Tree shrew

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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