Effect of the antihistamine, methapyrilene, as an initiator of hepatocarcinogenesis in female rats.
The antihistamine methapyrilene was examined for its ability to initiate hepatocarcinogenesis in rats. Rats were first subjected to partial hepatectomy and then were intubated with one of four doses (30, 100, 200 or 300 mg/kg) of methapyrilene hydrochloride (or an equivalent amount of water for controls, or 10 mg diethylnitrosamine/kg for positive controls). Rats were then fed 0.05% phenobarbital in the diet for 3, 6 or 9 months. The number and volume of altered hepatic foci were quantified with the histochemical markers gamma-glutamyl transpeptidase, glucose-6-phosphatase, and ATPase. The number of foci induced was increased 2- to 4-fold by the highest dose of methapyrilene at all 3 time points, but the only statistically significant increase was produced by the 200 mg/kg dose after 3 months of promotion. This study shows that methapyrilene may act as a weak initiator.
Glauert
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HP
Department of Nutrition and Food Science, University of Kentucky, Lexington 40506.
Pitot
H C
HC
D000251:Adenosine Triphosphatases / Q000032:analysis; D000631:Aminopyridines / Q000633:toxicity*; D000818:Animals; D005260:Female; D005952:Glucose-6-Phosphatase / Q000032:analysis; D006498:Hepatectomy; D006651:Histocytochemistry; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology; D008701:Methapyrilene / Q000633:toxicity*; D010634:Phenobarbital / Q000494:pharmacology; D010641:Phenotype; D051381:Rats; D011916:Rats, Inbred F344; D005723:gamma-Glutamyltransferase / Q000032:analysis
D000631:Aminopyridines; D008701:Methapyrilene; D005723:gamma-Glutamyltransferase; D005952:Glucose-6-Phosphatase; D000251:Adenosine Triphosphatases; D010634:Phenobarbital