Reduction of aflatoxin B(1) adduct biomarkers by oltipraz in the tree shrew (Tupaia belangeri chinensis)

Cancer Lett. 2000 Jun 1;154(1):79-83. doi: 10.1016/s0304-3835(00)00382-7.


The risk of liver cancer is greatest in people both infected with hepatitis B virus (HBV) and highly exposed to aflatoxin B(1) (AFB(1)). The tree shrew (Tupaia belangeri chinensis) is a unique species that can be infected with human HBV, is susceptible to AFB(1)-induced liver cancer, and shows a synergistic interaction between HBV and AFB(1) 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 microg AFB(1)/kg b.wt. in milk daily for 4 weeks. One week prior to AFB(1) 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-N(7)-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 AFB(1) 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 AFB(1) dosing, oltipraz treatment decreased urinary aflatoxin-N(7)-guanine by 93%. Collectively, these results indicate that oltipraz reduces AFB(1) 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, AFB(1) exposed tree shrews.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aflatoxin B1 / blood
  • Aflatoxin B1 / metabolism*
  • Aflatoxin B1 / urine
  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Antiviral Agents / pharmacology*
  • Biomarkers
  • Chromatography, High Pressure Liquid
  • DNA Adducts / blood
  • DNA Adducts / metabolism*
  • DNA Adducts / urine
  • Female
  • Hepatitis B virus / metabolism
  • Humans
  • Liver Neoplasms / chemically induced
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / prevention & control
  • Liver Neoplasms / virology
  • Male
  • Pyrazines / pharmacology*
  • Radioimmunoassay
  • Thiones
  • Thiophenes
  • Time Factors
  • Tupaiidae / metabolism*


  • Anticarcinogenic Agents
  • Antiviral Agents
  • Biomarkers
  • DNA Adducts
  • Pyrazines
  • Thiones
  • Thiophenes
  • oltipraz
  • Aflatoxin B1