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Specific examples of methylation in detoxification: Arsenic detoxification requires sequential methylation: arsenite to monomethylarsonic acid to dimethylarsinic acid (the excretable form), catalyzed by arsenic methyltransferase (AS3MT) using SAM-e R Mercury undergoes methylation by gut bacteria, converting inorganic mercury to more toxic methylmercury (this is detrimental methylation, not detoxification) R COMT methylation of 4-hydroxy catechol estrogens prevents them from forming reactive quinones that generate ROS and DNA damage R 6

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Supplementary Figure 8 (A, B) Cumulative data showing relative concentrations of decreased metabolites in the R vs A group