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S58
Strategies for chemoprevention of liver cancer
Thomas W Kensler,
Patricia A Egner, Jin-Bing Wang, Yuan-Rong Zhu, Bao-Chu
Zhang, Geng-Sun Qian, Shuang-Yuan Kuang, Stephen J Gange,
Lisa P Jacobson, Alvaro Munoz, John D Groopman
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.
Key words:
Aflatoxin, chemoprevention, liver cancer, oltipraz,
chlorophyllin, phase 2 enzymes, clinical trials,
biomarkers
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