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ANALYSIS OF THE MECHANISM OF METHYLMERCURY CYTOTOXICITY
Citation:
Massaro, E., R. Zucker, AND K. Elstein. ANALYSIS OF THE MECHANISM OF METHYLMERCURY CYTOTOXICITY. U.S. Environmental Protection Agency, Washington, D.C., EPA/600/D-90/042 (NTIS PB90221748).
Description:
We have investigated MeHg-induced perturbation of the cell cycle kinetics of the murine erythroleukemic cell (MELC) by flow cytometry (FCM). e observed that, at-relatively low levels (2.5 - 7.5 uM), MeHg predominately inhibits progression through the S phase of the cell cycle (in a dose-dependent manner). ccumulation of cells in the G2/M phase of the cycle also occurs, but to a considerably lesser extent. ight microscopy reveals a dose-dependent increase in incidence of chromosomal aberrations (condensation, pulverization). igher dose levels (10 - 50 uM) induce chromosomal ring formation and progressive perturbation of the cell membrane/cytoplasm complex. he latter is manifested as increased 900 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). ur 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.