Response of CHO cell proliferation and histone phosphorylation to sodium arsenite
Because of the causal association between arsenic and cancer in humans, studies were initiated to determine whether low levels of arsenic affect cell proliferation and chromatin constituents. Cultured CHO cells were treated with As(III) or As(V) in the form of sodium arsenite (NaAsO/sub 2/) or sodium arsenate (Na/sub 2/HAsO/sub 4/), respectively. Arsenite was 10 times more toxic than arsenate. At lower concentrations, 10 ..mu..M NaAsO/sub 2/ induced culture growth kinetics that were radiomimetic. During this division delay, histone Hl phosphorylation was reduced to 40% of the control level. It recovered to the control level just before recovery of cell division. Histone H2A phosphorylation was stimulated in the middle of the delay period, followed by stimulation of H3 phosphorylation just before recovery of cell division. ATP pool levels were unaffected at these low arsenite concentrations. The DNA synthesis rate was also reduced during division delay, but it did not recover immediately before resumption of cell division. Flow microfluorometric analysis showed that cell cycle progression was inhibited in G/sub 1/, S, and G/sub 2/ during the division delay period. On recovery of cell division, cells in S and G/sub 2/ regained the capacity to resume cycle traverse earlier than did cells in G/sub 1/. Cell survival studies indicated that 89% of the cells survived 24-h treatment with 10 ..mu..M NaAsO/sub 2/.
- Research Organization:
- Los Alamos Scientific Lab., NM
- OSTI ID:
- 5098808
- Journal Information:
- J. Toxicol. Environ. Health; (United States), Vol. 6:1
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ARSENIC COMPOUNDS
BIOLOGICAL EFFECTS
CELL CYCLE
INHIBITION
PHOSPHORYLATION
ANIMAL CELLS
ATP
BIOSYNTHESIS
CELL DIVISION
CELL PROLIFERATION
CHROMATIN
DNA
GENETIC EFFECTS
HISTONES
KINETICS
NEOPLASMS
TOXICITY
CHEMICAL REACTIONS
DISEASES
NUCLEIC ACIDS
NUCLEOTIDES
ORGANIC COMPOUNDS
PROTEINS
SYNTHESIS
560301* - Chemicals Metabolism & Toxicology- Cells- (-1987)
550300 - Cytology
550200 - Biochemistry