Analysis of the mechanism of methyl mercury cytotoxicity
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), decreased axial light loss (cell size), simultaneous propidium iodide and carboxyfluorescein fluorescence, and resistance to detergent (NP-40)-mediated cytolysis. 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.
- Research Organization:
- Environmental Protection Agency, Research Triangle Park, NC (USA). Health Effects Research Lab.
- OSTI ID:
- 6714183
- Report Number(s):
- PB-90-221748/XAB; EPA-600/D-90/042
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
METHYLMERCURY
TOXICITY
CELL CYCLE
CELL FLOW SYSTEMS
CELL MEMBRANES
CHROMOSOMAL ABERRATIONS
CYTOPLASM
DNA REPLICATION
DOSE-RESPONSE RELATIONSHIPS
GENETIC EFFECTS
MITOSIS
SURVIVAL TIME
BIOLOGICAL EFFECTS
CELL CONSTITUENTS
CELL DIVISION
MEMBRANES
MERCURY COMPOUNDS
MUTATIONS
NUCLEIC ACID REPLICATION
ORGANIC COMPOUNDS
ORGANIC MERCURY COMPOUNDS
560300* - Chemicals Metabolism & Toxicology