title: In vitro studies of DNA damage and its repair in cells from NHL patients with different p53 mutant protein status, resistant (p53(+)) and sensitive (p53(-)) to cancer chemotherapy.
abstract: BACKGROUND
  Resistance to an anthracycline-based regimen, such as CHOP, constitutes a problem for curing non-Hodgkin's lymphoma (NHL) patients. Chemoresistance in the clinic manifests itself as a lack of response to treatment or regrowth of a tumour after an initial response.
  
  
  METHODS
  In this study, lymphocytes from NHL patients were treated with hydrogen peroxide (H(2)O(2)), a free radical generating model agent, and ethyl methanesulfonate (EMS), a model alkylating agent, to induce DNA damage which was evaluated by SCGE. This study assessed whether or not there were any differences in the patterns of damage and repair between cells from patients with p53 mutant protein abnormalities, i.e. over-expression (p53(+)) not responding to the CHOP regimen and patients responding to the CHOP regimen without p53 protein abnormalities (p53(-)) by comparison with control individuals (wild-type). An NHL cell line model [Raji TK(+) (mex(+)) and TK(-) (mex(-))] with p53 over-expression was also investigated.
  
  
  RESULTS
  Results showed that frozen/thawed samples from healthy people were not suitable for use in repair studies, whilst fresh samples or samples incubated for 20 h at room temperature could be used. Tumour cells were more sensitive to damage than control cells. After treatment with H(2)O(2), cells from fresh or incubated blood showed a similar repair capacity. After treatment with EMS, there was a difference between repair in resistant and sensitive cells.
  
  
  CONCLUSIONS
  These results suggest that the repair process is a useful cellular biomarker for investigating chemoresistance. The lack of repair in p53(+) cells may correlate with a low level of MGMT, since there was no repair in the Raji TK(-) cells lacking this enzyme.
authors.affiliation: Department of Biomedical Sciences, School of Life Sciences, University of Bradford BD7 1DP, UK.
authors.forename: Behzad
authors.initials: B
authors.lastname: Foroutan
authors.forename: Afruj
authors.initials: A
authors.lastname: Ali Ruf
authors.forename: David
authors.initials: D
authors.lastname: Jerwood
authors.forename: Diana
authors.initials: D
authors.lastname: Anderson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000627:therapeutic use; D004249:DNA Damage; D004260:DNA Repair; D004317:Doxorubicin / Q000008:administration & dosage / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005020:Ethyl Methanesulfonate / Q000494:pharmacology; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D014750:Vincristine / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D005020:Ethyl Methanesulfonate; D006861:Hydrogen Peroxide; D011241:Prednisone