Immunocytochemical visualization of DNA adducts in mouse tissues and human white blood cells following treatment with benzo[a]pyrene or its diol epoxide. A quantitative approach

Carcinogenesis. 1991 Mar;12(3):427-33. doi: 10.1093/carcin/12.3.427.

Abstract

The formation and stability of benzo[a]pyrene DNA adducts were studied in tissues of BALB/c mice exposed to benzo[a]pyrene (B[a]P). The DNA adducts were visualized with an immunocytochemical peroxidase staining technique using an antiserum specific for the major B[a]P-derived adduct in DNA [(+/-)trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10- tetrahydrobenzo[a]pyrene (BPDE-N2-dG)]. The nuclear staining density was measured by microdensitometry. When mice were treated with an increasing dose of B[a]P the nuclear staining increased in the tissues studied (lung, heart and kidney). A linear relationship was found between the immunocytochemical nuclear staining signal and the actual DNA adduct level in the lung as measured by 32P-postlabeling. Maximum adduct formation was found 5 days after a single i.p. injection of B[a]P. Adduct levels decreased gradually after 7 days, but even after 61 days a slight specific staining was still present, suggesting that not all adducts had disappeared at that time. As judged from the disappearance of [3H]thymidine from prelabeled DNA the loss of adducts from the lung was not a result of DNA repair but one of cell turnover. In human white blood cells B[a]P-derived adducts could be detected after in vitro incubation with the reactive metabolite of B[a]P (BPDE). Dose-response studies demonstrated a positive relationship between BPDE-DNA adduct formation, the immunocytochemical staining signal and the BPDE concentration in the culture medium.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / metabolism*
  • Animals
  • Benzo(a)pyrene / metabolism*
  • Cells, Cultured
  • DNA / metabolism*
  • DNA Adducts*
  • Densitometry / methods
  • Dihydroxydihydrobenzopyrenes / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Immunohistochemistry
  • Kidney / metabolism
  • Leukocytes / cytology
  • Leukocytes / metabolism*
  • Lung / metabolism
  • Male
  • Mice
  • Mice, Inbred Strains
  • Myocardium / metabolism
  • Phosphorus Radioisotopes

Substances

  • 7,8-dihydroxy-9,10-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene-DNA adduct
  • DNA Adducts
  • Dihydroxydihydrobenzopyrenes
  • Phosphorus Radioisotopes
  • benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA
  • benzo(a)pyrene-DNA adduct
  • Benzo(a)pyrene
  • 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
  • DNA