Reduction of aflatoxin B(1) adduct biomarkers by oltipraz in the tree shrew (Tupaia belangeri chinensis).
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.
Li
Y
Y
Department of Pathology, Guangxi Cancer Institute, Nanning, China.
Su
J
J
Qin
L
L
Egner
P A
PA
Wang
J
J
Groopman
J D
JD
Kensler
T W
TW
Roebuck
B D
BD
D016604:Aflatoxin B1 / Q000097:blood / Q000378:metabolism* / Q000652:urine; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D015415:Biomarkers; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D006515:Hepatitis B virus / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control / Q000821:virology; D008297:Male; D011719:Pyrazines / Q000494:pharmacology*; D011863:Radioimmunoassay; D013871:Thiones; D013876:Thiophenes; D013997:Time Factors; D014418:Tupaiidae / Q000378:metabolism*
D016588:Anticarcinogenic Agents; D000998:Antiviral Agents; D015415:Biomarkers; D018736:DNA Adducts; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; C026209:oltipraz; D016604:Aflatoxin B1