Synergistic effects of phenobarbital and thiourea on proliferative lesions in the rat liver.
To evaluate the effects of phenobarbital (PB) and thiourea (TU), alone or in combination, on proliferative lesions of the liver, thyroid and lung, male F344 rats initiated with 2000 mg/kg body weight N-bis(2-hydroxypropyl) nitrosamine (DHPN) were given diet and/or drinking water containing 0% PB/TU (group 1), 1000 ppm PB (group 2), 0.1% TU (group 3) and 500 ppm PB and 0.05% TU (group 4), from weeks 2 to 20 for 19 weeks. Group 4 showed remarkable increases in the number of hepatocellular altered foci per animal, the values being superior to the averages of groups 2 and 3. The number of thyroid proliferative lesions per animal was highest in group 3 and lowest in group 2. Lung proliferative lesions were induced in all groups, but no modifying influence on their development was evident in the combined group. The present results indicate that combined administration of PB and TU exerts synergistic enhancing effects on hepatocarcinogenesis.
Shimo
T
T
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
Mitsumori
K
K
Onodera
H
H
Yasuhara
K
K
Kitaura
K
K
Takahashi
M
M
Kanno
J
J
Hayashi
Y
Y
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D009602:Nitrosamines; D010634:Phenobarbital / Q000633:toxicity*; D011230:Precancerous Conditions / Q000139:chemically induced*; D051381:Rats; D011916:Rats, Inbred F344; D013890:Thiourea / Q000633:toxicity*; D013961:Thyroid Gland / Q000187:drug effects / Q000473:pathology
D009602:Nitrosamines; C012457:diisopropanolnitrosamine; D013890:Thiourea; D010634:Phenobarbital