Inhibition of DNA Methylation

Procainamide and hydralazine were found to inhibit DNA methylation (Cornacchia et al. 1988). DNA methylation inhibits gene transcription, and so inhibition of DNA methylation could lead to lymphocyte activation. This is an attractive mechanism for the induction of lupus, and it does not require the formation of a reactive metabolite. However, it is conceivable that it is a reactive metabolite that is responsible for inhibition of DNA methylation. Decreased DNA methylation has also been reported in idiopathic lupus (Richardson et al. 1990). In unpublished studies, we found other drugs that inhibited DNA methylation to the same extent as procainamide, and yet the drugs involved are not associated with drug-induced lupus. Even if inhibition of DNA methylation is not the exclusive mechanism of drug-induced lupus, it may make a significant contribution to the mechanism for some drugs.

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