Summary
Male Sprague-Dawley rats were treated for 7 weeks with 120 mg/l N-nitrosomorpholine in their drinking water. At the end of the treatment period there were large numbers of enzyme-altered foci in the liver. During the following 10 weeks, the number of foci decreased significantly. This decrease in the number of enzyme-altered foci was due to the disappearance of a special type of focus. The typical features of these non-persisting foci were distinct enzyme histochemical and striking morphological alterations as well as the localization in or close to the third zone, as defined by Rappaport. In contrast to the simultaneously appearing persisting foci, the non-persisting foci were always glycogen-poor or totally glycogenfree. Signs of cell death were frequently found in or near this type of focus. After these non-persisting foci had disappeared, the total number of pre-neoplastic lesions obviously remained constant. We conclude that this disappearance of early appearing, severely altered foci is due to cell loss caused by the non-specific toxic effect of the carcinogen.
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References
Bannasch P (1968) The cytoplasm of hepatocytes during carcinogenesis. Rec Res Cancer Res 19:1–100
Bannasch P, Hesse J, Angerer H (1974) Hepatozelluläre Glykogenose und die Genese sogenannter hyperplastischer Knoten in der Thioacetamid-vergifteten Rattenleber. Virchows Arch (Zellpathol) 17:29–50
Bannasch P, Mayer D, Hacker HJ (1980) Hepatocellular glycogenosis and hepatocarcinogenesis. Biochim Biophys Acta 605:217–245
Bannasch P, Hacker HJ, Klimek F, Mayer D (1984) Hepatocellular glycogenosis and related pattern of enzymatic changes during hepatocarcinogenesis. Adv Enzyme Regul 22:97–121
Bannasch P, Zerban H, Hacker HJ (1985) Foci of altered hepatocytes, rat, 10–30. In: Jones TC, Mohr U, Hunt RD (eds) Monographs on pathology of laboratory animals, digestive system. Springer, Berlin Heidelberg New York, pp 10–30
Barbason H, Fridman-Manduzio A, Lelievre P, Betz EH (1977) Variations of liver cell control during diethylnitrosamine carcinogenesis. Eur J Cancer 13:13–18
Buchmann A, Kuhlmann WD, Schwarz M, Kunz HW, Wolf CR, Moll E, Friedberg T, Oesch F (1985) Regulation and expression of four cytochrome P-450 isoenzymes, NADPH-cytochrome P-450 reductase, the glutathione transferase B and C and microsomal epoxide hydrolase in preneoplastic and neoplastic lesions in rat liver. Carcinogenesis 6:513–521
Bursch W, Lauer B, Timmermann-Trosiener I, Barthel G, Schuppler J, Schulte-Hermann R (1984) Controlled death (apoptosis) of normal and putative preneoplastic cells in rat liver following withdrawal of tumor promoters. Carcinogenesis 5:453–458
Emmelot P, Scherer E (1980) The first relevant cell stage in rat liver carcinogenesis. A quantitative approach. Biochim Biophys Acta 605:247–304
Enzmann H, Bannasch P (1987) Potential significance of phenotypie heterogeneity of focal lesions at different stages in hepatocarcinogenesis. Carcinogenesis 8:1607–1612
Enzmann H, Edler L, Bannasch P (1987) Simple elementary method for the quantification of focal liver lesions induced by carcinogens. Carcinogenesis 8:231–235
Farber E (1980) The sequential analysis of cancer induction. Biochim Biophys Acta 605:149–166
Farber E (1982) The biology of carcinogen-induced hepatocyte nodules and related liver lesions in the rat. Toxicol Pathol 10:197–205
Farber E (1984) Precancerous steps in carcinogenesis. Their physiological adaptive nature. Biochim Biophys Acta 738:171–180
Hacker HJ, Moore MA, Mayer D, Bannasch P (1982) Correlative histochemistry of some enzymes of carbohydrate metabolism in preneoplastic and neoplastic lesions in the rat liver. Carcinogenesis 3:1265–1272
Ito N, Moore MA, Bannasch P (1984) Modification of the development of N-nitrosomorpholine induced hepatic lesions by 2-acetylaminofluorene, phenobarbital and 4,4′-diaminodiphenylmethane: a sequential histological and histochemical analysis. Carcinogenesis 5:535–542
Kitagawa T (1971) Responsiveness of hyperplastic lesions and hepatomas to partial hepatectomy. Gann 62:217–224
Kitagawa T (1976) Sequential phenotypic changes in hyperplastic areas during hepatocarcinogenesis in the rat. Cancer Res 36:2534–2539
Moore MA, Hacker HJ, Bannasch P (1983) Phenotypic instability in focal and nodular lesions induced in a short term system in the rat liver. Carcinogenesis 4:595–603
Pitot HC, Sirica AE (1980) The stages of initiation and promotion in hepatocarcinogenesis. Biochim Biophys Acta 605:191–215
Rabes HM, Scholze P, Jantsch B (1972) Growth kinetics of diethylnitrosamine-induced enzyme-deficient “preneoplastic” liver cell populations in vivo and in vitro. Cancer Res 32:2577–2586
Scherer E (1984) Neoplastic progression in experimental hepatocarcinogenesis. Biochim Biophys Acta 738:219–236
Squire RA, Levitt MH (1975) Report of a workshop on classification of specific hepatocellular lesions in rats. Cancer Res 35:3214–3223
Stewart HL, Williams G, Keysser CH, Lombard LS, Montali RJ (1980) Histologic typing of liver tumors of the rat. J Natl Cancer Inst 65:179–206
Tatematsu M, Nagamine Y, Farber E (1983) Redifferentiation as a basis for remodeling of carcinogen-induced hepatocyte nodules to normal appearing liver. Cancer Res 43:5049–5058
Teebor GW, Becker FF (1971) Regression and presistence of hyperplastic nodules induced by N-2-fluorenylacetamide and their relationship to hepatocarcinogenesis. Cancer Res 31:1–3
Williams GM (1980) The pathogenesis of rat liver cancer caused by chemical carcinogens. Biochim Biophys Acta 605:167–189
Williams GM, Watanabe K (1978) Quantitative kinetics of development of N-2-fluorenylacetamide-induced, altered hyperplastic hepatocellular foci resistant to iron accumulation and of their reversion of persistence following removal of carcinogen. J Natl Cancer Inst 61:113–121
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Dedicated to Professor Werner Kunz on the occasion of his 65th birthday
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Enzmann, H., Bannasch, P. Non-persisting early foci of altered hepatocytes induced in rats by N-nitrosomorpholine. J Cancer Res Clin Oncol 114, 30–34 (1988). https://doi.org/10.1007/BF00390482
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DOI: https://doi.org/10.1007/BF00390482