Epigenetic effects are considered heritable but may also be modified by environmental factors. Arecoline (ARC), a major component of areca nut alkaloids, is an important environmental risk factor for oral cancer and hepatocellular carcinomain Taiwan. The aim of this study was to determine the influence of ARC on the epigenome. The mRNA expression of histone methyltransferases, acetyltransferases, and demethylases were assessed in K-562 cells following exposure to ARC. Results demonstrated that ARC produced changes in the expressions of several genes catalyzing histone methylation (Mll, Setdb1, and Suv39h2), acetylation (Atf2), and demethylation (JMJD6). Since H3K9 methylation is involved in maintaining the stability of heterochromatin structures and inactivating euchromatic gene expressions, data suggest that the ARC-induced epigenetic changes play a role in the mechanisms underlying chemical-mediated cytotoxicity and genotoxicity.

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Abstract:The radical copolymerizations of styrene (MI) with coumarin (M~) (and 7-acetoxycoumarin) have been first carried out in benzene (and in DMF) at 60 ° C using AIBN as initiator. The terminal model monomer reactivity ratios (MRR) were determined by Fineman-Ross method, Kelen-Tudos method and nonlinear method. The respective estimated values are r I = 43.08, re = 0.63; r l = 39.17, r2 = 0.43; and r l = 49.94, r2 = 1.04 for styrene-coumarin (S-C) system. For styrene-7-acetoxycoumarin (S-AC) system, the values are rl = 51.44, r2 = 1.24; r I = 50.56, r 2 = 1.20 and r I = 56.23, r2 = 1.48, respectively. The penultimate model MRRs are determined by Fenn-Barson method and nonlinear method to be Q= 49.18, r 1' = 2.01, r2 = r2' = 0.43 and r I = 51.21, rt' = 0.86, r2=r 2' =0, respectively, for S-C system; rl = 64.76, rl' = 3.46, r, = r2' = 1.20 and r I = 59.90, rl = 0.57, r2 = r2' =0. respectively, for S-AC system. It is found that coumarin is about 1.2 times more reactive toward styrene-terminated radical than 7-acetoxycoumarin for steric reasons. The penultimate model of Fenn-Barson is fairly adequate in describing the copolymerization mechanism of styrene-coumarin system, while the terminal model is more suitable for styrene-7-acetoxycoumarin system.