Literature DB >> 11724948

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

P A Egner1, J B Wang, Y R Zhu, B C Zhang, Y Wu, Q N Zhang, G S Qian, S Y Kuang, S J Gange, L P Jacobson, K J Helzlsouer, G S Bailey, J D Groopman, T W Kensler.   

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-N(7)-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-N(7)-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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Year:  2001        PMID: 11724948      PMCID: PMC64728          DOI: 10.1073/pnas.251536898

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


  28 in total

1.  Identification and characterization of chlorin e(4) ethyl ester in sera of individuals participating in the chlorophyllin chemoprevention trial.

Authors:  P A Egner; K H Stansbury; E P Snyder; M E Rogers; P A Hintz; T W Kensler
Journal:  Chem Res Toxicol       Date:  2000-09       Impact factor: 3.739

Review 2.  A mutator phenotype in cancer.

Authors:  L A Loeb
Journal:  Cancer Res       Date:  2001-04-15       Impact factor: 12.701

3.  Protection against aflatoxin B1-induced hepatocarcinogenesis in F344 rats by 5-(2-pyrazinyl)-4-methyl-1,2-dithiole-3-thione (oltipraz): predictive role for short-term molecular dosimetry.

Authors:  B D Roebuck; Y L Liu; A E Rogers; J D Groopman; T W Kensler
Journal:  Cancer Res       Date:  1991-10-15       Impact factor: 12.701

4.  Base substitution mutations induced by metabolically activated aflatoxin B1.

Authors:  P L Foster; E Eisenstadt; J H Miller
Journal:  Proc Natl Acad Sci U S A       Date:  1983-05       Impact factor: 11.205

5.  Use of chlorophyllin in the care of geriatric patients.

Authors:  R W Young; J S Beregi
Journal:  J Am Geriatr Soc       Date:  1980-01       Impact factor: 5.562

6.  Specific p53 mutations detected in plasma and tumors of hepatocellular carcinoma patients by electrospray ionization mass spectrometry.

Authors:  P E Jackson; G S Qian; M D Friesen; Y R Zhu; P Lu; J B Wang; Y Wu; T W Kensler; B Vogelstein; J D Groopman
Journal:  Cancer Res       Date:  2001-01-01       Impact factor: 12.701

7.  Liquid chromatography electrospray-mass spectrometry of urinary aflatoxin biomarkers: characterization and application to dosimetry and chemoprevention in rats.

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Journal:  Chem Res Toxicol       Date:  2001-07       Impact factor: 3.739

8.  Chlorophyllin chemoprevention in trout initiated by aflatoxin B(1) bath treatment: An evaluation of reduced bioavailability vs. target organ protective mechanisms.

Authors:  V Breinholt; D Arbogast; P Loveland; C Pereira; R Dashwood; J Hendricks; G Bailey
Journal:  Toxicol Appl Pharmacol       Date:  1999-07-15       Impact factor: 4.219

9.  Identification of aflatoxins by quadrupole mass spectrometry/mass spectrometry.

Authors:  R D Plattner; G A Bennett; R D Stubblefield
Journal:  J Assoc Off Anal Chem       Date:  1984 Jul-Aug

10.  Excretion of an aflatoxin-guanine adduct in the urine of aflatoxin B1-treated rats.

Authors:  R A Bennett; J M Essigmann; G N Wogan
Journal:  Cancer Res       Date:  1981-02       Impact factor: 12.701

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  59 in total

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Journal:  Food Addit Contam Part A Chem Anal Control Expo Risk Assess       Date:  2010-05

2.  Cancer chemoprevention by dietary chlorophylls: a 12,000-animal dose-dose matrix biomarker and tumor study.

Authors:  Tammie J McQuistan; Michael T Simonich; M Margaret Pratt; Cliff B Pereira; Jerry D Hendricks; Roderick H Dashwood; David E Williams; George S Bailey
Journal:  Food Chem Toxicol       Date:  2011-11-03       Impact factor: 6.023

3.  Modulation of the metabolism of airborne pollutants by glucoraphanin-rich and sulforaphane-rich broccoli sprout beverages in Qidong, China.

Authors:  Thomas W Kensler; Derek Ng; Steven G Carmella; Menglan Chen; Lisa P Jacobson; Alvaro Muñoz; Patricia A Egner; Jian Guo Chen; Geng Sun Qian; Tao Yang Chen; Jed W Fahey; Paul Talalay; John D Groopman; Jian-Min Yuan; Stephen S Hecht
Journal:  Carcinogenesis       Date:  2011-11-01       Impact factor: 4.944

4.  cis-Terpenones as an effective chemopreventive agent against aflatoxin B1-induced cytotoxicity and TCDD-induced P450 1A/B activity in HepG2 cells.

Authors:  Qibing Zhou; Hang Xie; Lin Zhang; Jennifer K Stewart; Xing-Xing Gu; John J Ryan
Journal:  Chem Res Toxicol       Date:  2006-11       Impact factor: 3.739

5.  Role of dietary supplements/nutraceuticals in chemoprevention through induction of cytoprotective enzymes.

Authors:  Jed W Fahey; Thomas W Kensler
Journal:  Chem Res Toxicol       Date:  2007-03-16       Impact factor: 3.739

6.  Prevention of hepatocellular carcinoma.

Authors:  Michael C Kew
Journal:  HPB (Oxford)       Date:  2005       Impact factor: 3.647

Review 7.  Chemopreventive strategies in hepatocellular carcinoma.

Authors:  Siddharth Singh; Preet Paul Singh; Lewis R Roberts; William Sanchez
Journal:  Nat Rev Gastroenterol Hepatol       Date:  2013-08-13       Impact factor: 46.802

8.  The dietary phytochemical chlorophyllin alters E-cadherin and beta-catenin expression in human colon cancer cells.

Authors:  Orianna Carter; George S Bailey; Roderick H Dashwood
Journal:  J Nutr       Date:  2004-12       Impact factor: 4.798

9.  Identifying efficacious approaches to chemoprevention with chlorophyllin, purified chlorophylls and freeze-dried spinach in a mouse model of transplacental carcinogenesis.

Authors:  David J Castro; Christiane V Löhr; Kay A Fischer; Katrina M Waters; Bobbie-Jo M Webb-Robertson; Roderick H Dashwood; George S Bailey; David E Williams
Journal:  Carcinogenesis       Date:  2008-12-10       Impact factor: 4.944

10.  Effects of chlorophyll and chlorophyllin on low-dose aflatoxin B(1) pharmacokinetics in human volunteers.

Authors:  Carole Jubert; John Mata; Graham Bench; Roderick Dashwood; Cliff Pereira; William Tracewell; Kenneth Turteltaub; David Williams; George Bailey
Journal:  Cancer Prev Res (Phila)       Date:  2009-12-01
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