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DNA Interstrand Cross-linking, Repair, and SCE Mechanism in Human Cells in Special Reference to Fanconi Anemia

  • Yoshisada Fujiwara
  • Yoshio Kano
  • Yoko Yamamoto

Abstract

The relation of DNA cross-linking and repair to sister chromatid exchange (SCE) formation was studied in normal human, Fanconi anemia (FA), and xeroderma pigmentosum (XP) cells. Despite a hypersensitive lethality response in FA cells, the SCE induction rates by mitomycin C (MMC), trimethylpsoralen (TMP)-light, cisplatin, and diepoxybutane were twice as high as in normal cells. For MMC, the induced SCE frequency in normal cells was reduced in a biphasic fashion with a repair incubation time (the first decline t1/2 = 2 hr; the second t1/2 = 14–18 hr) which corresponds exactly to the molecular kinetics of 1/2cross-link and monoadduct removal. However, FA cells lack the first half-excision process and exhibit a lack of the first rapid decline SCE component. The slow decline component is present, and a higher SCE frequency is observed 24 to 48 hr after treatment. By contrast, XP cells capable of the half-excision process reveal the first rapid decline component, followed by an extremely slow second-reduction component (t1/2 = 48 hr) due to defective monoadduct repair. The endoreduplicatiσn-SCE method revealed that rates of both twin (first cycle) and single (second cycle) SCE formations by MMC and TMP-light were higher in FA cells than in normal cells. These results indicate that cross-links remaining unrepaired induce SCEs as do monoadducts. The probabilistic SCE induction occurs at a rate of 1 SCE per 35 MMC cross-links in FA cells. Further, a non-SCE-forming tolerance mechanism also operates in hypersensitive FA cells. These molecular and cytogenetic results allow us to construct a new probabilistic model for cross-link-induced SCE into which the replication-fork model, random cross-link transfer to both chromatids, and chromatid breakage-reunion are incorporated.

Keywords

Fanconi Anemia Xeroderma Pigmentosum Fanconi Anemia Cell Xeroderma Pigmentosum Cell Sister Chroma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • Yoshisada Fujiwara
    • 1
  • Yoshio Kano
    • 1
  • Yoko Yamamoto
    • 1
  1. 1.Department of Radiation BiophysicsKobe University School of MedicineChuo-ku, Kobe 650Japan

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