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Inhibition of DNA Synthesis in Caco-2 Cells by Oxidative Stress (Amelioration by Epidermal Growth Factor)

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Abstract

The role of oxidative stress in the regulationof intestinal epithelial proliferation was examined byevaluating the effect of H2O2andxanthine oxidase + xanthine (XO + X) on[3H]thymidine incorporation into DNA in Caco-2 cells. DNAsynthesis was highest 4 and 5 days after seeding, whileit declined rapidly between 5 and 12 days. Pretreatmentfor 0.5-24 h with H2O2or XO + X reduced DNA synthesis on 4- to6-day-old, but not on 7- to 20-day-old cells. The effectof XO + X on DNA synthesis was significantly reduced bycatalase, superoxide dismutase, and ferric chloride, but pretreatment with deferoxamine potentiatedXO + X-induced inhibition of DNA synthesis.Coadministration of epidermal growth factor (EGF) for 24hr reduced the H2O2and XO +X-induced inhibition of DNA synthesis; this effect of EGFwas not observed up to 8 hr. Results show thatO2-and H2O2rapidlyinhibit DNA synthesis in Caco-2 cells and that EGFrestores DNA synthesis in oxidant-treatedcells.

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Authors
  1. J. A. Engler
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  2. A. Gupta
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  3. R. K. Rao
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Engler, J.A., Gupta, A. & Rao, R.K. Inhibition of DNA Synthesis in Caco-2 Cells by Oxidative Stress (Amelioration by Epidermal Growth Factor). Dig Dis Sci 44, 1902–1909 (1999). https://doi.org/10.1023/A:1018815327769

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