Quantitative morphometric comparison between the expression of two different "marker enzymes" in preneoplastic liver lesions induced in rats with low doses of N-nitrosodiethanolamine.
Male Sprague-Dawley rats were treated with low doses of N-nitrosodiethanolamine (NDELA) (0.2, 0.63, 1.5, 6 and 25 mg/kg body wt per day). Foci of altered hepatocytes developed at all dose levels. The extent of foci positive for gamma-glutamyl transpeptidase (gamma-GT), as demonstrated histochemically in frozen sections, was quantitated morphometrically and compared with the data obtained earlier in the same livers by measuring the extent of foci positive for glucose-6-phosphate dehydrogenase (G6PDH). The area density of foci positive for gamma-GT was much smaller than that of foci positive for G6PDH at all dose levels and time points studied. However, there was an increase in the area density of both gamma-GT- and G6PDH-positive foci proportionally to the time of treatment and the total dose of the carcinogen administered. The dose-time relation for the induction of 0.5% gamma-GT positive liver tissue assessed as a double logarithmic plot gives a straight line. The same holds true for the induction of 1% G6PDH-positive liver tissue. The slopes of these straight lines are identical, and they have the same characteristics as the line indicating the time when 50% of the animals developed liver tumors at higher doses. Thus, a close statistical correlation of enzyme altered hepatic foci and the development of hepatocellular tumor exists irrespective of the absolute amount of the area density of the respective foci.
Zerban
H
H
Institut für experimentelle Pathologie, Deutsches Krebsforschungszentrum, Heidelberg, F.R.G.
Preussmann
R
R
Bannasch
P
P
D000818:Animals; D004052:Diethylnitrosamine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005954:Glucosephosphate Dehydrogenase / Q000032:analysis; D008113:Liver Neoplasms / Q000139:chemically induced / Q000201:enzymology*; D008297:Male; D011230:Precancerous Conditions / Q000139:chemically induced / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains; D005723:gamma-Glutamyltransferase / Q000032:analysis
C014129:N-nitrosodiethanolamine; D004052:Diethylnitrosamine; D005954:Glucosephosphate Dehydrogenase; D005723:gamma-Glutamyltransferase