Lack of potential of low dose N-nitrosodimethylamine to induce preneoplastic lesions, glutathione S-transferase placental form-positive foci, in rat liver
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- 作者：Fukushima ; Shoji ; Wanibuchi ; Hideki ; Morimura ; Keiichirou ; Nakae ; Dai ; Tsuda ; Hiroyuki ; Imaida ; Katsumi ; et. al.
- 关键词：N-nitrosodimethylamine ; Risk assessment ; Carcinogenicity dose threshold
- 刊名：Cancer Letters
- 出版年：2005
- 出版时间：May 10, 2005
- 年：2005
- 卷：222
- 期：1
- 页码：11-15
- 全文大小：110 K
文摘
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.