Induction of hepatocellular carcinoma with high metastatic potential in WS/Shi rats: discovery of an inbred strain highly susceptible to the liver carcinogen N-nitrosomorpholine.
We investigated the susceptibility of three inbred strains of rats to the hepatocarcinogen, N-nitrosomorpholine (NNM), to establish a spontaneous metastatic model of hepatocellular carcinoma (HCC). WS/Shi. SD/gShi, and F344/DuCrj rats were given 0.02% NNM in drinking water for 8 weeks and thereafter left without any treatment. The experiment ceased at week 20, because mortality markedly increased after this time point in WS/Shi rats. Liver weight was highest in WS/Shi rats among the three strains examined. The incidence of HCC was 15/15 (100%) in WS/Shi rats, 1/16 (6%) in SD/gShi rats, and 13/16 (81%) in F344/DuCrj rats surviving after NNM treatment. Metastasis to the lung was observed in HCC-bearing rats at an incidence of 13/15 (87%) in WS/Shi, 1/1 in SD/gShi, and 6/13 (46%) in F344/DuCrj. Four-week administration of NNM resulted in a significantly higher BrdU-labeling index of hepatocytes in WS/Shi rats than in the other strains. These findings indicated that WS/Shi is the most sensitive strain to NNM and may be the most suitable strain for use as a spontaneous metastatic model of HCC among the strains of rats examined in the present study.
Murai
T
T
First Department of Pathology Osaka City University Medical School, Osaka, Japan. takashi murai@shionogi.co.jp
Mori
S
S
Hosono
M
M
Iwakura
Y
Y
Takashima
A
A
Oohara
T
T
Makino
S
S
Takeda
R
R
Fukushima
S
S
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D004198:Disease Susceptibility; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008175:Lung Neoplasms / Q000556:secondary*; D008297:Male; D009602:Nitrosamines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D013045:Species Specificity
D002273:Carcinogens; D009602:Nitrosamines; C002741:N-nitrosomorpholine