TY - JOUR
T1 - Lack of potential of low dose N-nitrosodimethylamine to induce preneoplastic lesions, glutathione S-transferase placental form-positive foci, in rat liver
AU - Fukushima, Shoji
AU - Wanibuchi, Hideki
AU - Morimura, Keiichirou
AU - Nakae, Dai
AU - Tsuda, Hiroyuki
AU - Imaida, Katsumi
AU - Shirai, Tomoyuki
AU - Tatematsu, Masae
AU - Tsukamoto, Tetsuya
AU - Hirose, Masao
AU - Furukawa, Fumio
N1 - Funding Information:
This research was supported by a grant from the Japan Science and Technology Corporation, included in the Project of Core Research for Evolutional Science and Technology (CREST), and a Grant-in-Aid for Specially Promoted Research from the Ministry of Education, Science, Sports, Culture and Technology of Japan. The authors would also like to acknowledge the encouragement of Dr N. Ito (Emeritus Prof., Nagoya City University Medical School, Nagoya, Japan) and Dr T. Kitagawa (Director, Cancer Institute, Tokyo, Japan).
PY - 2005/5/10
Y1 - 2005/5/10
N2 - 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.
AB - 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.
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U2 - 10.1016/j.canlet.2004.08.035
DO - 10.1016/j.canlet.2004.08.035
M3 - Article
C2 - 15837536
AN - SCOPUS:20244387173
SN - 0304-3835
VL - 222
SP - 11
EP - 15
JO - Cancer Letters
JF - Cancer Letters
IS - 1
ER -
