Title of article :
Lack of potential of low dose N-nitrosodimethylamine to induce preneoplastic lesions, glutathione S-transferase placental form-positive foci, in rat liver
Author/Authors :
Fukushima، نويسنده , , Shoji and Wanibuchi، نويسنده , , Hideki and Morimura، نويسنده , , Keiichirou and Nakae، نويسنده , , Dai and Tsuda، نويسنده , , Hiroyuki and Imaida، نويسنده , , Katsumi and Shirai، نويسنده , , Tomoyuki and Tatematsu، نويسنده , , Masae and Tsukamoto، نويسنده , , Tetsuya and Hirose، نويسنده , , Masao and Furukawa، نويسنده , , Fumio، نويسنده ,
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.
