Cytogenetic evaluations in human lymphocytes exposed to methyl acetimidate, a lysine-specific protein crosslinking...

The cytogenetic effects of methyl acetimidate (MAI), a lysine-specific protein crosslinking reagent, were investigated using human peripheral lymphocytes in culture. Lymphocytes were treated with the chemical either prior to PHA exposure or 2-3 days following mitogenic stimulation and assessed for perturbations in cellular proliferation and induction of SCEs. Severe reductions in the mitotic index (MI) and pronounced decreases in the proportion of metaphases proceeding beyond M(1) were observed following G0 exposure to MAI concentrations of as low as 2 mM; with complete suppression of mitotic activity in all cultures exposed to levels of 3 mM MAI or greater. Concentrations resulting in severe depression in MI caused only moderate increases in SCEs. Cells exposed to less than 10 mM MAI during the late S-G2 stages of the cell cycle and harvested at the first metaphase following treatment exhibited profound mitotic delay, impaired prophase to metaphase transitions and abnormal mitotic configurations. These findings demonstrate that protein-specific crosslinking agents may induce a wide spectrum of adverse cytogenetic outcomes in both cycling and noncycling lymphocytes.