Dose-dependent benzo(a)pyrene [B(a)P]-DNA adduct levels and persistence in F-344 rats following subchronic dietary exposure to B(a)P

Cancer Lett. 2006 Aug 28;240(2):268-78. doi: 10.1016/j.canlet.2005.09.016. Epub 2005 Nov 8.

Abstract

In order to investigate the relationship between BaP-DNA adduct formation and long-term exposure to benzo(a)pyrene (BaP), DNA adduct levels in liver and lung tissues of male and female F-344 rats subchronically exposed to BaP were determined. Doses of 0, 5, 50, and 100mg/kg BaP, representing control, low, intermediate, and high doses, respectively, were administered in the animal diet over a 90-day period. After dosing, animals were sacrificed, liver and lung tissues were removed, DNA was isolated and analyzed for BaP-induced DNA adducts by the (32)P-postlabeling method using a four-directional thin-layer chromatography system. At low and intermediate BaP doses, DNA adduct levels in the tissues were significantly correlated with exposure. However, at high BaP doses, the dose-DNA adduct relationship became non-linear. Similarly, the relative DNA adducts persistence at intermediate and high doses were significantly higher than that measured at low dose. The low and intermediate dose linearity and high dose non-linearity may be due to saturation of metabolic activation and detoxification enzymes, and DNA repair processes.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Benzo(a)pyrene / metabolism
  • Benzo(a)pyrene / toxicity*
  • Carcinogens, Environmental / toxicity*
  • DNA Adducts / metabolism*
  • Diet*
  • Female
  • Liver / drug effects
  • Liver / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Male
  • Phosphorus Radioisotopes
  • Rats
  • Rats, Inbred F344

Substances

  • Carcinogens, Environmental
  • DNA Adducts
  • Phosphorus Radioisotopes
  • benzo(a)pyrene-DNA adduct
  • Benzo(a)pyrene