The mechanism of cytotoxicity of methylmercury: Inhibition of progression through the S phase of the cell cycle

The effect of methylmercury (MeHg) on progression of the murine erythroleukemic cell (MELC) through the cell cycle was analyzed by flow cytometry (FCM). Exposure in vitro to 5.0-10.0 μmol dm^?3 MeHg for 6h resulted in a dose-dependent decrease in the rate of cell replication, apparently as a result of inhibition of DNA synthesis (rate of passage through the S phase of the cell cycle). Thus, only a modest accumulation of cells with a G₂/M (4n) DNA content was observed. At or above 10 μmol dm^?3 MeHg, progression through all phases of the cell cycle was blocked. FCM revealed a dose-dependent increase in cellular refractive index (90° light scatter), decrease in apparent cell volume (axial light loss), and increase in resistance to non-ionic detergent (NP-40)-mediated cytolysis indicative of fixation (protein denaturation, cross-linking, etc.) of the plasma membrane/cytoplasm complex. The data indicate DNA synthesis as the primary target of MeHg cytotoxicity.