Analysis of 4-ABP-DNA adducts and p53 alterations in urinary bladder carcinoma

Anticancer Res. 1999 Sep-Oct;19(5C):4571-6.

Abstract

Background: Activated intermediates of 4-aminobiphenyl (4-ABP) are able to covalently interact with DNA to form adducts. There is a large body of evidence indicating that carcinogen-DNA adduct formation can be one of the cancer initiating mechanisms.

Materials and methods: (4-ABP)-induced DNA damage in association with p53 overexpression and mutations were evaluated in specimens of urothelial bladder cancers from 106 patients.

Results: 4-ABP-DNA adduct levels resulted higher in smokers compared to non smokers, with a borderline statistical value. p53 nuclear overexpression was related to tumor grading, while no significant correlation with stage, 4-ABP-DNA adducts, smoking habit, and disease recurrence could be observed. Concerning molecular analysis, p53 point mutations were found in 17 of 106 cases (16%) and mutational pattern was significantly associated both with higher grade and stage, but no correlation was found with disease recurrence.

Conclusions: These results suggest that other sources, in addition to tobacco smoke, may contribute to 4-ABP-DNA adducts formation in bladder tissue and that p53 expression/mutation cannot be considered a prognostic factor in bladder cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminobiphenyl Compounds / metabolism*
  • Carcinogens / metabolism*
  • DNA Adducts*
  • DNA, Neoplasm / metabolism*
  • Humans
  • Neoplasm Staging
  • Point Mutation
  • Smoking / genetics*
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / metabolism
  • Urinary Bladder Neoplasms / pathology

Substances

  • Aminobiphenyl Compounds
  • Carcinogens
  • DNA Adducts
  • DNA, Neoplasm
  • Tumor Suppressor Protein p53
  • 4-biphenylamine