Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthrene tetraols in a randomized clinical trial in He Zuo township, Qidong, People's Republic of China.
Residents of Qidong, People's Republic of China, are at high risk for development of hepatocellular carcinoma, in part due to consumption of aflatoxin-contaminated foods, and are exposed to high levels of phenanthrene, a sentinel of hydrocarbon air toxics. Cruciferous vegetables, such as broccoli, contain anticarcinogens. Glucoraphanin, the principal glucosinolate in broccoli sprouts, can be hydrolyzed by gut microflora to sulforaphane, a potent inducer of carcinogen detoxication enzymes. In a randomized, placebo-controlled chemoprevention trial, we tested whether drinking hot water infusions of 3-day-old broccoli sprouts, containing defined concentrations of glucosinolates, could alter the disposition of aflatoxin and phenanthrene. Two hundred healthy adults drank infusions containing either 400 or < 3 micromol glucoraphanin nightly for 2 weeks. Adherence to the study protocol was outstanding; no problems with safety or tolerance were noted. Urinary levels of aflatoxin-N(7)-guanine were not different between the two intervention arms (P = 0.68). However, measurement of urinary levels of dithiocarbamates (sulforaphane metabolites) indicated striking interindividual differences in bioavailability. An inverse association was observed for excretion of dithiocarbamates and aflatoxin-DNA adducts (P = 0.002; R = 0.31) in individuals receiving broccoli sprout glucosinolates. Moreover, trans, anti-phenanthrene tetraol, a metabolite of the combustion product phenanthrene, was detected in urine of all participants and showed a robust inverse association with dithiocarbamate levels (P = 0.0001; R = 0.39), although again no overall difference between intervention arms was observed (P = 0.29). Understanding factors influencing glucosinolate hydrolysis and bioavailability will be required for optimal use of broccoli sprouts in human interventions.
Kensler
Thomas W
TW
Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Room E7541, 615 North Wolfe Street, Baltimore, MD 21205, USA. tkensler@jhsph.edu
Chen
Jian-Guo
JG
Egner
Patricia A
PA
Fahey
Jed W
JW
Jacobson
Lisa P
LP
Stephenson
Katherine K
KK
Ye
Lingxiang
L
Coady
Jamie L
JL
Wang
Jin-Bing
JB
Wu
Yan
Y
Sun
Yan
Y
Zhang
Qi-Nan
QN
Zhang
Bao-Chu
BC
Zhu
Yuan-Rong
YR
Qian
Geng-Sun
GS
Carmella
Stephen G
SG
Hecht
Stephen S
SS
Benning
Lorie
L
Gange
Stephen J
SJ
Groopman
John D
JD
Talalay
Paul
P
D000328:Adult; D000348:Aflatoxins / Q000378:metabolism / Q000652:urine*; D000368:Aged; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001628:Beverages; D001682:Biological Availability; D001937:Brassica / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000517:prevention & control; D018736:DNA Adducts / Q000652:urine*; D005260:Female; D005961:Glucosinolates / Q000494:pharmacology*; D006801:Humans; D006868:Hydrolysis; D008113:Liver Neoplasms / Q000209:etiology / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D010616:Phenanthrenes / Q000652:urine*; D010919:Placebos
D000348:Aflatoxins; D016588:Anticarcinogenic Agents; D018736:DNA Adducts; D005961:Glucosinolates; D010616:Phenanthrenes; D010919:Placebos