Inhibition of DNA synthesis by chromium compounds.
J Toxicol Environ Health 1985 Jan; 15(2):237-244
The effects of hexavalent and trivalent chromium (7440473) (Cr) on DNA synthesis were studied in-vitro. Mouse L-cells before or after permeabilization in a Triton-X-100 buffer were incubated with up to 1000 micromolar (microM) potassium-dichromate (7778509) or up to 3.3 millimolar (mM) chromic-trichloride (10025737) for 2 hours. The effects on DNA synthesis were evaluated by measuring uptake of tritium labeled thymidine. A system consisting of 100 micrograms per milliliter calf thymus DNA plus 2 to 40 units per milliliter DNA- polymerase was incubated with up to 20mM potassium-dichromate or chromic-chloride. The effects on DNA synthesis were determined as before. Cr+6 caused a dose dependent inhibition of DNA synthesis in intact L-cells. The concentration causing 50% inhibition (IC50) was 10microM. The inhibitory effect was irreversible as removal of the Cr+6 from the medium did not result in the level of DNA synthesis returning to the control value. Cr+3 did not inhibit DNA synthesis. Both Cr+3 and Cr+6 inhibited DNA synthesis to about the same extent in Triton-X-100 permeabilized cells. The IC50 for each was approximately 33microM. Cr+3 showed a steep S-shaped dose response curve, whereas inhibition by Cr+6 was linear. Cr+3 inhibited DNA synthesis in the DNA/DNA-polymerase system biphasically. Concentrations below 0.1 to 1mM enhanced DNA synthesis; higher concentrations decreased the level of synthesis. Cr+6 caused a weak monophasic inhibition of DNA synthesis. Increasing the concentration of DNA-polymerase in the system reversed the inhibitory effect of Cr+6, but not that of Cr+3.
NIOSH-Publication; NIOSH-Grant; Grants-other; Nucleic-acids; Biosynthesis; Hexavalent-chromium-compounds; Chromium-compounds; Dose-response; In-vitro-studies; Mammalian-cells; Physiological-chemistry
Pharmacology University of Kansas 39Th St at Rainbow Blvd Kansas City, Kansas 66103
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Journal of Toxicology and Environmental Health
University of Kansas Col Hlth Sci & Hosp, Kansas City, Kansas