Lack of potential of low dose N-nitrosodimethylamine to induce preneoplastic lesions, glutathione S-transferase placental form-positive foci, in rat liver

Shoji Fukushima, Hideki Wanibuchi, Keiichirou Morimura, Dai Nakae, Hiroyuki Tsuda, Katsumi Imaida, Tomoyuki Shirai, Masae Tatematsu, Tetsuya Tsukamoto, Masao Hirose, Fumio Furukawa

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Induction of liver lesions in male F344 rats by the genotoxic and carcinogenic N-nitrosodimethylamine (NDMA) was studied at a wide range of dose levels, i.e. from 0.001 to 10 ppm, in drinking water for 16 weeks. Dose related and statistically significant increase of glutathione S-transferase placental form-positive foci, endpoint markers for hepatocarcinogenesis in rats, at 1 and 10 ppm dose groups was obtained, but no increment in foci could be detected with the lower doses (0.001, 0.01, and 0.1 ppm). This finding of a no-observed effect level supports our hypothesis that a threshold, at least in practical terms, exists in carcinogenesis proposed on the basis of extensive wide range dose-dependence studies of other genotoxic carcinogens.

Original languageEnglish
Pages (from-to)11-15
Number of pages5
JournalCancer Letters
Volume222
Issue number1
DOIs
Publication statusPublished - 10-05-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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