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Time- and dose-dependent DNA binding of PAHs derived from diesel particle extracts, benzo[a]pyrene and 5-methychrysene in a human mammary carcinoma cell line (MCF-7).

Abstract
Cultures of a human mammary carcinoma cell line (MCF-7) were exposed to the soluble organic fraction of diesel particle emissions, benzo[a]pyrene (B[a]P) and 5-methylchrysene (5-MeCHR) to study time- and dose-related PAH-DNA binding. The concentrations of 14 PAHs in three extracts were analyzed by HPLC and PAH-DNA adducts were measured by (32)P post-labeling assay. Time-dependent DNA adducts formation of 2.5 microM B[a]P was lower than that of 2.5 microM 5-MeCHR. In comparison with B[a]P, 2-fold higher adduct formation by 5-MeCHR was observed at 12 h exposure, after which BPDE adducts decreased and 5-MeCHR continued to form adducts linearly during 48 h exposure. The data for these two PAH compounds demonstrate a large variation in adduct-forming potency, which should be taken into account when estimating DNA adducts formed by mixtures of unknown PAHs. A clear dose-response effect on formation of DNA adducts was obtained for B[a]P and a Standard Reference Material (SRM) of diesel particulate matter. The amount of B[a]P contributed more to total DNA adduct formation by SRM than by three diesel extracts. Thus, no conclusions can be drawn from diesel particle-derived B[a]P as to the adduct-forming potency of other carcinogenic PAHs. There was little change in adduct levels formed by three diesel extracts from 0 to 12 h exposure. Thereafter, the number of adducts formed by RD2 increased more rapidly than those formed by RD1 and EN97. The concentrations of 14 PAHs and adduct levels analyzed at 24 and 48 h did not change in the same proportion between the extracts. Neither could PAH-DNA adduct levels be explained by the sum of strong and weak adduct-forming PAHs analyzed in the extracts. This indicates that other PAHs in the extracts RD1, RD2 and EN97 contributed to adduct formation more than the carcinogenic adduct-forming PAHs analyzed in this study.
AuthorsT Kuljukka-Rabb, K Peltonen, S Isotalo, S Mikkonen, L Rantanen, K Savela
JournalMutagenesis (Mutagenesis) Vol. 16 Issue 4 Pg. 353-8 (Jul 2001) ISSN: 0267-8357 [Print] England
PMID11420405 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Carcinogens
  • Chrysenes
  • DNA Adducts
  • DNA, Neoplasm
  • Gasoline
  • Benzo(a)pyrene
  • 5-methylchrysene
Topics
  • Benzo(a)pyrene (metabolism, toxicity)
  • Breast Neoplasms (metabolism)
  • Carcinogenicity Tests
  • Carcinogens (metabolism)
  • Chrysenes (metabolism, toxicity)
  • DNA Adducts (analysis)
  • DNA, Neoplasm (metabolism)
  • Dose-Response Relationship, Drug
  • Female
  • Gasoline (toxicity)
  • Humans
  • Risk Factors
  • Time Factors
  • Tumor Cells, Cultured

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