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Published on: August 31, 2022
Global hypomethylation in hepatocellular carcinoma and its relationship to aflatoxin B(1) exposure
Yu-Jing Zhang1, Hui-Chen Wu, Hulya Yazici
1Yu-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.
Aim:
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).
Conclusion:
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.
