Comparison of various immunochemical assays for the detection of ethylene oxide-DNA adducts with monoclonal antibodies against imidazole ring-opened N7-(2-hydroxyethyl)guanosine: application in a biological monitoring study

Carcinogenesis. 1994 Sep;15(9):1867-73. doi: 10.1093/carcin/15.9.1867.

Abstract

Monoclonal antibodies have been developed for the analysis of the predominant lesion in DNA induced by ethylene oxide (EtOx), namely N7-(2-hydroxyethyl)guanine (N7-EtOHGua). Two monoclonal antibodies raised against imidazole ring-opened N7-(2-hydroxyethyl)guanine (RON7-EtOHGua), N7EO-E and N7EO-11, and the previously isolated antibody N7E-102 were characterized by competitive ELISA with various inhibitors. N7EO-E and N7EO-11 recognize 2-hydroxyethyl lesions better than ethyl or methyl lesions, while N7E-102 recognizes 2-hydroxyethyl and ethyl modifications equally well. All antibodies show a preference for imidazole ring-opened adducts, bind better to adducts in DNA compared to alkylated nucleosides or bases and bind 10(6)- to 3 x 10(6)-fold less well to unmodified DNA. The sensitivity of detection of RON7-EtOHGua in DNA and in the nuclei of cells in situ by antibody N7EO-E was investigated in several assays. The immunoslot blot assay was the most sensitive method (0.34 RON7-EtOHGua per 10(6) nucleotides was detectable), followed by competitive ELISA, direct ELISA and in situ detection by immunofluorescence microscopy. The immunoslot blot assay was used to analyse N7-EtOHGua levels in white blood cell DNA from individuals exposed to EtOx (2-5 p.p.m.) and of controls. This exposure did not result in a statistically significant increase in the N7-EtOHGua level.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / immunology
  • Antibodies, Monoclonal* / isolation & purification
  • Antibody Specificity
  • Cell Nucleus / chemistry
  • DNA / analysis*
  • DNA / drug effects
  • DNA / metabolism
  • DNA Adducts / analysis*
  • DNA Adducts / metabolism
  • DNA Damage
  • Enzyme-Linked Immunosorbent Assay
  • Ethylene Oxide / analysis*
  • Ethylene Oxide / metabolism
  • Ethylene Oxide / toxicity
  • Guanine / analogs & derivatives*
  • Guanine / immunology
  • Guanine / metabolism
  • Humans
  • Immunohistochemistry
  • Leukocytes / chemistry
  • Male
  • Mice
  • Mice, Inbred Strains
  • Microscopy, Fluorescence
  • Occupational Exposure
  • Sensitivity and Specificity

Substances

  • Antibodies, Monoclonal
  • DNA Adducts
  • N(7)-hydroxyethylguanine
  • Guanine
  • DNA
  • Ethylene Oxide