Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer

Patricia Egner, Jin Bing Wang, Yuan Rong Zhu, Bao Chu Zhang, Yan Wu, Qi Nan Zhang, Geng Sun Qian, Shuang Yuan Kuang, Stephen J Gange, Lisa Paula Jacobson, Kathy J. Helzlsouer, George S. Bailey, John Davis Groopman, Thomas W Kensler

Research output: Contribution to journalArticle

Abstract

Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N7-guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography-electrospray mass spectrometry. This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N7-guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.

Original languageEnglish (US)
Pages (from-to)14601-14606
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number25
DOIs
StatePublished - Dec 4 2001

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Aflatoxins
DNA Adducts
Liver Neoplasms
Placebos
Guanine
Chlorophyll
Hepatocellular Carcinoma
Food Coloring Agents
Biomarkers
Food
chlorophyllin
Chemoprevention
Liquid Chromatography
Carcinogens
Biological Availability
Meals
Chromatography
China
Mass Spectrometry
Animal Models

ASJC Scopus subject areas

  • Genetics
  • General

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Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. / Egner, Patricia; Wang, Jin Bing; Zhu, Yuan Rong; Zhang, Bao Chu; Wu, Yan; Zhang, Qi Nan; Qian, Geng Sun; Kuang, Shuang Yuan; Gange, Stephen J; Jacobson, Lisa Paula; Helzlsouer, Kathy J.; Bailey, George S.; Groopman, John Davis; Kensler, Thomas W.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 98, No. 25, 04.12.2001, p. 14601-14606.

Research output: Contribution to journalArticle

Egner, Patricia ; Wang, Jin Bing ; Zhu, Yuan Rong ; Zhang, Bao Chu ; Wu, Yan ; Zhang, Qi Nan ; Qian, Geng Sun ; Kuang, Shuang Yuan ; Gange, Stephen J ; Jacobson, Lisa Paula ; Helzlsouer, Kathy J. ; Bailey, George S. ; Groopman, John Davis ; Kensler, Thomas W. / Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer. In: Proceedings of the National Academy of Sciences of the United States of America. 2001 ; Vol. 98, No. 25. pp. 14601-14606.
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abstract = "Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N7-guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography-electrospray mass spectrometry. This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N7-guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55{\%} reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.",
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T1 - Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer

AU - Egner, Patricia

AU - Wang, Jin Bing

AU - Zhu, Yuan Rong

AU - Zhang, Bao Chu

AU - Wu, Yan

AU - Zhang, Qi Nan

AU - Qian, Geng Sun

AU - Kuang, Shuang Yuan

AU - Gange, Stephen J

AU - Jacobson, Lisa Paula

AU - Helzlsouer, Kathy J.

AU - Bailey, George S.

AU - Groopman, John Davis

AU - Kensler, Thomas W

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N2 - Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N7-guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography-electrospray mass spectrometry. This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N7-guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.

AB - Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part from consumption of foods contaminated with aflatoxins. Chlorophyllin, a mixture of semisynthetic, water-soluble derivatives of chlorophyll that is used as a food colorant and over-the-counter medicine, has been shown to be an effective inhibitor of aflatoxin hepatocarcinogenesis in animal models by blocking carcinogen bioavailability. In a randomized, double-blind, placebo-controlled chemoprevention trial, we tested whether chlorophyllin could alter the disposition of aflatoxin. One hundred and eighty healthy adults from Qidong were randomly assigned to ingest 100 mg of chlorophyllin or a placebo three times a day for 4 months. The primary endpoint was modulation of levels of aflatoxin-N7-guanine adducts in urine samples collected 3 months into the intervention measured by using sequential immunoaffinity chromatography and liquid chromatography-electrospray mass spectrometry. This aflatoxin-DNA adduct excretion product serves as a biomarker of the biologically effective dose of aflatoxin, and elevated levels are associated with increased risk of liver cancer. Adherence to the study protocol was outstanding, and no adverse events were reported. Aflatoxin-N7-guanine could be detected in 105 of 169 available samples. Chlorophyllin consumption at each meal led to an overall 55% reduction (P = 0.036) in median urinary levels of this aflatoxin biomarker compared with those taking placebo. Thus, prophylactic interventions with chlorophyllin or supplementation of diets with foods rich in chlorophylls may represent practical means to prevent the development of hepatocellular carcinoma or other environmentally induced cancers.

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