Quantitative study of stereospecific binding of monoclonal antibody to anti-benzo(a)pyrene diol epoxide-N(2)-dG adducts by capillary electrophoresis immunoassay

J Chromatogr A. 2010 Apr 9;1217(15):2254-61. doi: 10.1016/j.chroma.2010.02.024. Epub 2010 Feb 20.

Abstract

The stereospecific binding of monoclonal antibody (mAb) 8E11 to anti-benzo(a)pyrene diol epoxide (BPDE)-dG adducts in single nucleoside, long oligonucleotide, and genomic DNA were quantitatively evaluated using noncompetitive and competitive capillary electrophoresis (CE) immunoassays. Two single-stranded TMR-BPDE-90 mers containing a single anti-BPDE-dG adduct with defined stereochemistry and a fluorescent label at 5'-end were used as fluorescent probes for competitive CE immunoassay. To quantitatively evaluate the binding affinity through competitive CE immunoassays, a series of equations were derived according to the binding stoichiometry. The binding of mAb 8E11 to trans-(+)-anti-BPDE-dG displays strongest affinity (K(b): 3.57 x 10(8) M(-1)) among all four investigated anti-BPDE-dG mononucleoside adducts, and the cis-(-)-anti-BPDE-dG displays lowest affinity (K(b): 1.14 x10(7) M(-1)). The binding of monoclonal antibody (mAb) 8E11 to BPDE-dG adducts in long DNA (90 mer) preferentially forms the complex with a stoichiometry of 1:1, and that mAb 8E11 displays a slightly higher affinity with trans-(+)-anti-BPDE-90 mers (K(b): 6.36+/-0.54 x 10(8)M(-1)) than trans-(-)-anti-BPDE-90 mers (K(b): 4.52+/-0.52 x 10(8) M(-1)). The mAb 8E11 also displays high affinity with BPDE-dG adducts in genomic DNA (K(b): 3.74 x 10(8) M(-1)), indicating its promising applications for sensitive immuno-detection of BPDE-DNA adducts in genomic DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / analogs & derivatives*
  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / chemistry
  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / metabolism
  • Antibodies, Monoclonal / metabolism*
  • Binding, Competitive
  • Cell Line, Tumor
  • DNA Adducts / metabolism*
  • Deoxyguanosine / analogs & derivatives*
  • Deoxyguanosine / chemistry
  • Deoxyguanosine / metabolism
  • Electrophoresis, Capillary / methods*
  • Fluorescence
  • Genome, Human / genetics
  • Humans
  • Immunoassay / methods*
  • Lasers
  • Linear Models
  • Rhodamines / metabolism
  • Stereoisomerism

Substances

  • Antibodies, Monoclonal
  • DNA Adducts
  • Rhodamines
  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • tetramethylrhodamine
  • 7,8-dihydroxy-9,10-epoxide-7,8,9,10-tetrahydrobenzo(a)pyrene-10-deoxyguanosine
  • Deoxyguanosine