Induction and removal of interstrand crosslinks in the ribosomal RNA genes of lymphoblastoid cell lines from patients with Fanconi anemia

Mutat Res. 1993 Oct;289(2):171-80. doi: 10.1016/0027-5107(93)90067-p.

Abstract

The repair of interstrand crosslinks has been investigated in Fanconi anemia (FA) and normal cells as there is evidence suggesting that FA patients have a defect in DNA repair. Lymphoblasts were treated with the crosslinking agent mitomycin C (MMC) and the removal of the induced DNA lesions investigated at the level of the actively transcribed ribosomal RNA (rRNA) genes. MMC-induced crosslinks appeared to be a rather stable lesion in the rRNA genes for all cell lines studied. Variable repair efficiencies were found between the different cells lines but they could not be used to distinguish normal cells from FA cells. Therefore, we propose that the specific sensitivity of FA cells towards MMC cannot be directly correlated with a deficient repair in interstrand crosslinks and that probably the complexity of the repair process is greater than previously described.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoradiography
  • Cell Line, Transformed
  • Cross-Linking Reagents
  • DNA Damage
  • DNA Repair*
  • DNA, Ribosomal / chemistry
  • DNA, Ribosomal / metabolism*
  • Dose-Response Relationship, Drug
  • Fanconi Anemia / genetics*
  • Humans
  • Lymphocytes
  • Mitomycin / toxicity
  • Nucleic Acid Denaturation
  • RNA, Ribosomal / genetics*
  • Structure-Activity Relationship

Substances

  • Cross-Linking Reagents
  • DNA, Ribosomal
  • RNA, Ribosomal
  • Mitomycin