Strategies for chemoprevention of liver cancer.
Liver cancer is one of the most common cancers worldwide. Infection with hepatitis B virus and exposure to aflatoxins in the diet act synergistically to amplify risk. From a public health perspective, hepatitis virus vaccination programs and efforts to both reduce aflatoxin exposures and to attenuate the toxicological consequences of unavoidable exposures should have major impacts on the incidence of this disease. Experimentally, aflatoxin-induced hepatocarcinogenesis can be inhibited by over a score of different chemopreventive agents with multiple mechanisms of action. One agent, oltipraz, is a potent inducer of phase 2 enzymes involved in the detoxication of carcinogens including aflatoxin. A second agent, chlorophyllin, impedes the bioavailability of carcinogens by forming molecular complexes and enhances their elimination in the fecal stream. This review highlights the findings of recent randomized clinical trials with oltipraz and chlorophyllin conducted in individuals exposed to dietary aflatoxins and at high risk for development of liver cancer. Both chemopreventive agents modulated levels of aflatoxin biomarkers in the study participants in manners consonant with protection.
Kensler
Thomas W
TW
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA. tkensler@jhsph.edu
Egner
Patricia A
PA
Wang
Jin-Bing
JB
Zhu
Yuan-Rong
YR
Zhang
Bao-Chu
BC
Qian
Geng-Sun
GS
Kuang
Shuang-Yuan
SY
Gange
Stephen J
SJ
Jacobson
Lisa P
LP
Muñoz
Alvaro
A
Groopman
John D
JD
D016588:Anticarcinogenic Agents / Q000008:administration & dosage*; D006528:Carcinoma, Hepatocellular / Q000517:prevention & control*; D018890:Chemoprevention / Q000379:methods*; D002735:Chlorophyllides / Q000008:administration & dosage*; D002986:Clinical Trials as Topic; D005260:Female; D005544:Forecasting; D006801:Humans; D008113:Liver Neoplasms / Q000517:prevention & control*; D008297:Male; D011322:Primary Prevention / Q000592:standards / Q000639:trends; D011379:Prognosis; D011719:Pyrazines / Q000008:administration & dosage*; D018570:Risk Assessment; D013871:Thiones; D013876:Thiophenes
D016588:Anticarcinogenic Agents; D002735:Chlorophyllides; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; C026209:oltipraz; C007020:chlorophyllin