Chemoprevention of hepatocellular carcinoma in aflatoxin
1: Gastroenterology. 2004 Nov;127(5 Suppl 2):S310-8.
Chemoprevention of hepatocellular carcinoma in aflatoxin endemic areas.
Kensler TW, Egner PA, Wang JB, Zhu YR, Zhang BC, Lu PX, Chen JG, Qian
GS, Kuang SY, Jackson PE, Gange SJ, Jacobson LP, Munoz A, Groopman JD.
Hepatocellular carcinoma 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 global 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. Although
pharmacological approaches establish proof of principle and help
identify key molecular targets for interventions, food-based approaches
that also use these molecular targets may be the most practical for
widespread application in high-risk populations.