The Reactivity of Selected Acrylate Esters toward Glutathione and Deoxyribonucleosides in Vitro: Structure-Activity Relationships

摘要: Acrylate esters are alpha,beta-unsaturated used as plastic monomers whose toxicity may involve reaction with tissue nucleophiles via Michael addition. Structure-activity relationships for reactivity of selected glutathione (GSH) and deoxyribonucleosides were investigated in the present studies. The methyl acrylate, methacrylate, ethyl butyl tetraethyleneglycol diacrylate, dimethacrylate, ethyleneglycol dimethacrylate. To compare their reactivities toward GSH, incubated up to 1 hr at 37 degrees C pH 7.4 either GSH or red blood cells phosphate-buffered saline followed by measurement free thiol. In both systems acrylate electrophilic decreased alpha-methyl substitution; however, decrease was more evident cell-free system than cell model. Increased alcohol chain length moderately affected apparent second-order rate constant spontaneous but did not affect potency relative cellular depletion. constants bifunctional twice much smaller monofunctional esters. Ethyl a reactive ester based upon alkylation, has been designated class 2B (suspect human) carcinogen International Agency Research on Cancer. detect possible DNA alkylation vitro, 24 6.7 8 50 C. HPLC analysis revealed no detectable adduct formation.(ABSTRACT TRUNCATED AT 250 WORDS)