Hepatocyte growth factor enhancement of preneoplastic hepatic foci development in rats treated with diethylnitrosamine and N-ethyl-N-hydroxyethylnitrosamine.
Effects of hepatocyte growth factor were investigated in a two-stage rat liver carcinogenesis protocol. Male F344 rats were first treated with diethylnitrosamine (200 mg/kg, i.p.) and then, starting two weeks later, with N-ethyl-N-hydroxyethylnitrosamine (EHEN) for 6 weeks at a dose of 0.01% in drinking water. Hepatocyte growth factor, which was injected i.v. at a dose of 200 micrograms/kg body weight one (at week 3) or two times (at weeks 3 and 4) during EHEN administration, significantly increased the development of preneoplastic glutathione S-transferase placental form-positive foci. Although the observed effects of hepatocyte growth factor were weaker than that of the two-thirds partial hepatectomy (PH) performed at week 3, the present results suggest that the enhancing effects of PH performed during the promotion stage may be largely mediated through induction of hepatocyte growth factor.
Yaono
M
M
First Department of Pathology, Nagoya City University Medical School.
Hasegawa
R
R
Mizoguchi
Y
Y
Futakuchi
M
M
Nakamura
T
T
Ito
N
N
Shirai
T
T
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D003043:Cocarcinogenesis; D004052:Diethylnitrosamine / Q000031:analogs & derivatives* / Q000633:toxicity*; D004357:Drug Synergism; D005982:Glutathione Transferase / Q000032:analysis; D006498:Hepatectomy; D017228:Hepatocyte Growth Factor / Q000633:toxicity*; D007668:Kidney / Q000033:anatomy & histology / Q000187:drug effects; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011230:Precancerous Conditions / Q000139:chemically induced* / Q000201:enzymology; D051381:Rats; D011916:Rats, Inbred F344
D002273:Carcinogens; C023845:N-ethyl-N-hydroxyethylnitrosamine; D004052:Diethylnitrosamine; D017228:Hepatocyte Growth Factor; D005982:Glutathione Transferase