Lack of potential of low dose N-nitrosodimethylamine to induce preneoplastic lesions, glutathione S-transferase placental form-positive foci, in rat liver.
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.
Fukushima
Shoji
S
Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan. fukuchan@med.osaka-cu.ac.jp
Wanibuchi
Hideki
H
Morimura
Keiichirou
K
Nakae
Dai
D
Tsuda
Hiroyuki
H
Imaida
Katsumi
K
Shirai
Tomoyuki
T
Tatematsu
Masae
M
Tsukamoto
Tetsuya
T
Hirose
Masao
M
Furukawa
Fumio
F
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004128:Dimethylnitrosamine / Q000633:toxicity*; D005982:Glutathione Transferase / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D008297:Male; D019055:No-Observed-Adverse-Effect Level; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D018570:Risk Assessment
D002273:Carcinogens; D005982:Glutathione Transferase; D004128:Dimethylnitrosamine