Global hypomethylation in hepatocellular carcinoma and its relationship to aflatoxin B(1) exposure.
OBJECTIVE
To determine global DNA methylation in paired hepatocellular carcinoma (HCC) samples using several different assays and explore the correlations between hypomethylation and clinical parameters and biomarkers, including that of aflatoxin B(1) exposure.


METHODS
Using the radio labeled methyl acceptance assay as a measure of global hypomethylation, as well as two repetitive elements, including satellite 2 (Sat2) by MethyLight and long interspersed nucleotide elements (LINE1), by pyrosequencing.


RESULTS
By all three assays, mean methylation levels in tumor tissues were significantly lower than that in adjacent tissues. Methyl acceptance assay log (mean ± SD) disintegrations/min/ng DNA are 70.0 ± 54.8 and 32.4 ± 15.6, respectively, P = 0.040; percent methylation of Sat2 42.2 ± 55.1 and 117.9 ± 88.8, respectively, P < 0.0001 and percent methylation LINE1 48.6 ± 14.8 and 71.7 ± 1.4, respectively, P < 0.0001. Aflatoxin B(1)-albumin (AFB(1)-Alb) adducts, a measure of exposure to this dietary carcinogen, were inversely correlated with LINE1 methylation (r = -0.36, P = 0.034).


CONCLUSIONS
Consistent hypomethylation in tumor compared to adjacent tissue was found by the three different methods. AFB(1) exposure is associated with DNA global hypomethylation, suggesting that chemical carcinogens may influence epigenetic changes in humans.
Yu-Jing Zhang, Hui-Chen Wu, Regina M Santella, Department of Environmental Health Sciences, Mailman School of Public Health of Columbia University, 630 W 168  St., New York, NY 10032, United States.
Yu-Jing
YJ
Zhang
Hui-Chen
HC
Wu
Hulya
H
Yazici
Ming-Whei
MW
Yu
Po-Huang
PH
Lee
Regina M
RM
Santella