Analysis of the Mechanism of Methylmercury Cytotoxicity

摘要

MeHg-induced perturbation of the cell cycle kinetics of the murine erythroleukemic cell (MELC) has been investigated by flow cytometry (FCM). It was observed that, at relatively low levels (2.5 - 7.5 microM), MeHg predominately inhibits progression through the S phase of the cell cycle (in a dose-dependent manner). Accumulation of cells in the G2/M phase of the cycle also occurs, but to a considerably lesser extent. Light microscopy reveals a dose-dependent increase in incidence of chromosomal aberrations (condensation, pulverization). Higher dose levels (10 - 50 microM), induce chromosomal ring formation and progressive perturbation of the cell membrane/cytoplasm complex. The latter is manifested as increased 90 deg light scatter (refractive index (Shapiro, 1988)), decreased axial light loss (cell size (Cambier and Monroe, 1983)), simultaneous propidium iodide and carboxyfluorescein fluorescence, and resistance to detergent (NP-40)-mediated cytolysis (Zucker et al., 1989). Observations indicate that DNA synthesis is the primary target of MeHg cytotoxicity and that apparent targets and degree of cytotoxicity are a complex function of dose.