Effect of varying the concentration of phenobarbital and its duration of treatment on the evolution of carcinogen induced enzyme-altered foci in rat liver.
The present study was aimed to investigate whether the promoting activity of phenobarbital in rodent liver is related to its daily dose level and duration of treatment or rather to its total dose administered. For this purpose groups of female Wistar rats were treated for 5 consecutive days with an initiating dose of 10 mg/kg body weight N-nitrosodiethylamine. Subsequently, rats were given phenobarbital-sodium (PB) in their drinking water at concentrations of 20, 50, 100 and 200 mg/l for varying lengths of time, such that the total dose of xenobiotic was very similar throughout the different treatment groups ranging from approximately 950 to 1100 mg/kg body weight. The number and volume fraction of lesions negative for the marker enzyme adenosine triphosphatase in liver were subsequently scored as a means to determine the carcinogenic response in this organ. Slight promoting effects of PB were only seen at the lowest concentration of 20 mg/l, whereas no significant effects were observed at 50 and 100 mg/l. At the highest concentration of 200 mg/l an inhibition of carcinogenic response was obtained. Although the effects seen in this study were only moderate, our data favour the idea that the promoting effects of PB depend on the actual concentration of the compound and the duration of treatment rather than on the total dose administered.
Appel
K E
KE
Bundesgesundheitsamt, Max von Pettenkofer Institute, Berlin, F.R.G.
Menden
M
M
Buchmann
A
A
Schwarz
M
M
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D004052:Diethylnitrosamine; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D010634:Phenobarbital / Q000378:metabolism / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains
D002273:Carcinogens; D004052:Diethylnitrosamine; D000251:Adenosine Triphosphatases; D010634:Phenobarbital