Chlorophyllin intervention reduces aflatoxin-DNA adducts in individuals at high risk for liver cancer.
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.
Egner
P A
PA
Department of Environmental Health Sciences and Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USA.
Wang
J B
JB
Zhu
Y R
YR
Zhang
B C
BC
Wu
Y
Y
Zhang
Q N
QN
Qian
G S
GS
Kuang
S Y
SY
Gange
S J
SJ
Jacobson
L P
LP
Helzlsouer
K J
KJ
Bailey
G S
GS
Groopman
J D
JD
Kensler
T W
TW
D000328:Adult; D016604:Aflatoxin B1 / Q000031:analogs & derivatives* / Q000652:urine; D000348:Aflatoxins / Q000633:toxicity* / Q000652:urine; D000368:Aged; D000818:Animals; D015415:Biomarkers / Q000652:urine; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000517:prevention & control*; D002681:China; D002735:Chlorophyllides / Q000494:pharmacology*; D018736:DNA Adducts / Q000187:drug effects* / Q000652:urine; D005260:Female; D005506:Food Contamination; D006147:Guanine / Q000031:analogs & derivatives* / Q000652:urine; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
D000348:Aflatoxins; D015415:Biomarkers; D002735:Chlorophyllides; D018736:DNA Adducts; C072611:aflatoxin B1-DNA adduct; D006147:Guanine; C028319:2,3-dihydro-2-(N(7)-guanyl)-3-hydroxyaflatoxin B1; D016604:Aflatoxin B1; C007020:chlorophyllin