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DNA adduct and tumor formations in rats after intratracheal administration of the urban air pollutant 3-nitrobenzanthrone.

Abstract
3-Nitrobenzanthrone (3-NBA) has been isolated from diesel exhaust and airborne particles and identified as a potent direct-acting mutagen in vitro and genotoxic agent in vivo. In order to evaluate the in vivo toxicity and carcinogenicity of 3-NBA in a situation corresponding to inhalation, a combined short-term and lifetime study with intratracheal (i.t.) instillation in female F344 rats was performed. DNA adduct formation, as a marker for the primary effect and analyzed by 32P-HPLC after single instillation, showed a few major DNA adducts and a rapid increase with a peak after 2 days, followed by a decline. No DNA adducts above the background level were observed after 16 days. The highest DNA adduct formation was observed in lung [approximately 250 DNA adducts/10(8) normal nucleotides (NN)] closely followed by kidney (approximately 200 DNA adducts/10(8) NN), whereas liver contained only 12% (approximately 30 DNA adducts/10(8) NN) of the levels of DNA adducts found in lung. In the tumor study, squamous cell carcinomas were found after 7-9 months in the high-dose group (total dose of 2.5 mg 3-NBA) and after 10-12 months in the low-dose group (total dose of 1.5 mg 3-NBA). The fraction of squamous cell carcinoma out of the total amount of tumors observed at the end of experiment at 18 months, corresponded to 3/16 and 11/16 in the low- and high-dose group, respectively. A single case of adenocarcinoma was also observed in each group. In the control group, no tumors were observed during the entire study of 18 months. In addition, a few cases of squamous metaplasia were also observed in the lung in both dose groups but not in the controls. In conclusion, 3-NBA forms DNA adducts in the lung immediately after i.t. administration but almost all DNA adducts were eliminated after 16 days. Tumor formation in two dose groups was observed in a dose-dependent manner with squamous cell carcinomas as the predominant tumor type at high exposure.
AuthorsEszter Nagy, Magnus Zeisig, Ken Kawamura, Yoshiharu Hisamatsu, Akiko Sugeta, Shuichi Adachi, Lennart Möller
JournalCarcinogenesis (Carcinogenesis) Vol. 26 Issue 10 Pg. 1821-8 (Oct 2005) ISSN: 0143-3334 [Print] England
PMID15917305 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Air Pollutants
  • Benz(a)Anthracenes
  • DNA Adducts
  • 3-nitrobenzanthrone
Topics
  • Air Pollutants (pharmacokinetics, toxicity)
  • Animals
  • Benz(a)Anthracenes (pharmacokinetics, toxicity)
  • DNA Adducts (drug effects, isolation & purification)
  • Female
  • Kidney (drug effects)
  • Liver (drug effects)
  • Lung (drug effects)
  • Rats
  • Rats, Inbred F344

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