2015 Volume 3 Issue 3 Pages 92-107
Methoxyacetate (MAA), formed by the metabolisms of ethylene glycol monomethyl ether (2-methoxyethanol), di-(2-methoxyethyl) phthalate and 1,6-dimethoxyhexane, is known to be a teratogenic and testicular toxicant in experimental animals. MAA is known to inhibit histone deacetylase and is associated with lactate-carrying monocarboxylate transporter expressed in Sertoli and fetal cells. In cells of rapid division, nucleosomal histone exchanges occur through the methyl and acetyl modifications and rates of nucleic acid syntheses are elevated with consumption of cellular energy. These phenomena are considered to associate with MAA-mediated teratogenicity and phase-selective spermatocyte disorders, and also suggest a mutual adverse-outcome pathway in which MAA-mediated histone deacetylase inhibition is involved through p21 activation as the early events. In addition, a possible functional relationship of one-carbon transferring folate/S-adenosyl methionine cycle with testicular metabolisms of sarcosine and creatine is envisioned. Thus, the mechanisms underlying the MAA toxicities will be discussed in relation to the current understanding of the involvement of the epigenetic phenomena and cell-specific metabolisms.
