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Inhibition of the development of hepatocellular carcinomas by phenyl N-tert-butyl nitrone in rats fed with a choline-deficient, L-amino acid-defined diet.

Abstract
Effects of phenyl N-tert-butyl nitrone (PBN), a spin-trapping agent, on the development of frank cancers were examined in male Wistar rats fed with a choline-deficient, l-amino acid-defined (CDAA) diet for 70 weeks. PBN (0.065% in the drinking water) reduced incidences, multiplicities and possibly sizes of both hepatocellular adenomas and carcinomas when administered for all 70 weeks or only for the first 26 weeks, and those of carcinomas but not adenomas, when administered only for the last 44 weeks. These results indicate that PBN can prevent the development of frank HCCs in the CDAA diet model. The anti-carcinogenic effect of PBN may be ascribed to the prevention of both the development of HCAs and their malignant conversion to HCCs. If such findings can be generalized, PBN may be able to serve as a good tool to investigate molecular mechanisms underlying carcinogenic processes.
AuthorsDai Nakae, Fumiyuki Uematsu, Hideki Kishida, Osamu Kusuoka, Shin-Ichi Katsuda, Midori Yoshida, Masakazu Takahashi, Akihiko Maekawa, Ayumi Denda, Yoichi Konishi, Yashige Kotake, Robert A Floyd
JournalCancer letters (Cancer Lett) Vol. 206 Issue 1 Pg. 1-13 (Mar 31 2004) ISSN: 0304-3835 [Print] Ireland
PMID15019154 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Amino Acids
  • Cyclic N-Oxides
  • Nitrogen Oxides
  • Water
  • phenyl-N-tert-butylnitrone
Topics
  • Adenoma (etiology, prevention & control)
  • Amino Acids (administration & dosage)
  • Animals
  • Body Weight (drug effects)
  • Carcinoma, Hepatocellular (etiology, prevention & control)
  • Choline Deficiency (complications)
  • Cyclic N-Oxides
  • Diet
  • Liver Neoplasms, Experimental (etiology, prevention & control)
  • Male
  • Nitrogen Oxides (toxicity)
  • Organ Size (drug effects)
  • Rats
  • Rats, Wistar
  • Water

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