Comparison of 32P-postlabeling and HPLC-FD analysis of DNA adducts in rats acutely exposed to benzo(a)pyrene

Chem Biol Interact. 1997 Apr 18;104(1):41-54. doi: 10.1016/s0009-2797(97)03765-4.

Abstract

DNA adduct analysis is often used for biomonitoring individuals exposed to polycyclic aromatic hydrocarbons (PAH). The 32P-postlabeling assay is routinely applied to study the formation of aromatic bulky adducts, but cannot positively identify individual adduct types. Recently, an HPLC assay with fluorescence detection (HPLC-FD) was developed which was sufficiently sensitive to detect adducts formed by benzo[a]pyrene (B[a]P) diolepoxide isomers [(+/-)anti- and (+/-)syn-BPDE] in occupationally exposed subjects (Rojas et al. Carcinogenesis, 16 (1995) 1373-1376). In this study, we compared both techniques using DNA samples of rats which were treated i.p. with B[a]P (10 mg/kg bw). The internal dose was assessed by measuring 3-OH-B[a]P excretion in urine. The detection limit of the HPLC-FD assay varied from 0.5 to 7.4 adducts per 10(8) nucleotides, while the detection limit of the 32P-postlabeling assay was around 1 adduct per 10(9) nucleotides. HPLC-FD analysis showed that BPDE-DNA adduct levels were highest in the heart, lung and liver respectively. The most predominant B[a]P-tetrol was the I-1 isomer, which derives from hydrolysis of the major reaction product of DNA and (+)-anti-BPDE. 32P-postlabeling analysis revealed an adduct spot that comigrated with a [3H]BPDE-DNA standard. The putative BPDE-DNA adduct levels were highest in heart followed by lung and liver and correlated significantly with tetrol I-1 levels determined by HPLC-FD (r = 0.72, P = 0.006). In samples in which both tetrol I-1 and II-2 were detected by means of HPLC-FD, this correlation was even better (r = 0.95, P = 0.01). Estimated half-lives of BPDE-DNA adducts were in the ranking order; heart, lung and liver for both techniques. By 32P-postlabeling, adducts other than BPDE-DNA were also found, resulting in highest total DNA adduct levels in the liver, heart and lung respectively. Furthermore, mean 24 h urinary excretion of 3-OH-B[a]P was related to BPDE-DNA adduct levels in lung, liver and heart. The 32P-postlabeling assay is sensitive and capable of detecting exposures to complex mixtures, whereas the HPLC-FD assay can be used to identify BPDE-isomers and might therefore be of value in risk assessment of individuals exposed to PAH.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Benzo(a)pyrene / analysis*
  • Benzo(a)pyrene / metabolism*
  • Benzopyrenes / metabolism
  • Carcinogens / metabolism
  • Chromatography, High Pressure Liquid
  • DNA / metabolism*
  • DNA Adducts / analysis*
  • Environmental Pollutants / metabolism
  • Fluorescence
  • Kinetics
  • Liver / chemistry
  • Lung / chemistry
  • Male
  • Myocardium / chemistry
  • Phosphorus Radioisotopes
  • Polycyclic Aromatic Hydrocarbons / metabolism
  • Rats
  • Rats, Inbred Lew
  • Urine / chemistry

Substances

  • Benzopyrenes
  • Carcinogens
  • DNA Adducts
  • Environmental Pollutants
  • Phosphorus Radioisotopes
  • Polycyclic Aromatic Hydrocarbons
  • benzo(a)pyrene-DNA adduct
  • Benzo(a)pyrene
  • 3-hydroxybenzo(a)pyrene
  • DNA