Summary
In order to clarify the underlying mechanism of malignant transformation from cirrhosis to hepatoma the cell kinetics of hepatocytes were studied in these two conditions. The content and synthesis of DNA in hepatocyte nuclei were investigated, by means of Feulgen-microspectrophotometry and tritiated thymidine radioautography, in cirrhotic and noncancerous parts of hepatoma with concomitant cirrhosis. The distribution of ploidy patterns was widely spread, from hypodiploid to hyperpolyploid, in the noncancerous parts of a cirrhotic liver containing hepatoma. In normal liver, each paired nuclear DNA content of a binucleate cell recorded almost the same amount, whereas in the noncancerous as well as in hepatoma cells much difference of DNA content was observed between the paired nuclei of the binucleate cells. The ploidy pattern of hepatocytes in patients with liver cirrhosis, who had developed hepatoma during follow-up periods of several months to several years, appeared to resemble that in noncancerous parts of hepatoma cases. On the other hand, the incorporation of tritiated thymidine into hepatocytes was found to be markedly increased in noncancerous parts as well as in cirrhotic liver developing hepatoma during follow-up periods. These results suggest the possibility that the hepatocytes in noncancerous parts of hepatoma have deranged cell-kinetics which might be a driving factor for the development of malignancy.
Similar content being viewed by others
References
Ashihara T, Kitamura O, Takeoka O, Kagawa K, Okuda K, Takino T, Fujita S (1977) Ploidy patterns of human liver cells in chronic liver diseases. Gastroenterology 73:1211
Böhm N, Sandritter W (1975) DNA in human tumor: A cytophotometric study. Curr Top Pathol 60:152–219
Daoust R, Calamai R (1971) Hyperbasophilic foci as sites of neoplastic transformation in hepatic parenchyma. Cancer Res 31:1290–1296
Epstein S, Ito N, Merkow L, Farber E (1967) Cellular analysis of liver carcinogenesis: The induction of larger hyperplastic nodules in the liver with 2-Fluorenylacetamide or ethionine and some aspects of their morphology and glycogen metabolism. Cancer Res 27:1702–1711
Farber E (1956) Similarities in the sequence of early histologic changes induced in the liver of the rat by ethionine, 2-acetylaminofluorene, and 3′-methyl-4-dimethylaminoazobenzene. Cancer Res 16:142–148
Farber E (1963) Ethionine carcinogenesis. Adv Cancer Res 7:383–474
Farber E (1968) On the concept of minimal deviation in the study of the biochemistry of cancer. Cancer Res 28:1210–1211
Furuta S, Koike Y, Nagata A, Kiyosawa K, Akahane Y, Yamamura S, Kawahara K, Komatsu H, Nakatani H, Miura M, Kamijyo K, Murayama S, Sodeyama T, Gibo Y, Iuchi M, Oda M (1979) Clinicopathological studies on the development of primary hepatocellular carcinoma. Follow up studies on 44 cases. (Japanese with English summary): Acta Hepatol Jpn 20:839–851
Hirose S, Iwase Z (1972) Analysis of the nuclear DNA content. A study on the nuclear DNA content of the borderline lesions between malignant and benign changes of the stomach. (Japanese). Jpn J Cancer Clin 18:859–869
Hitachi Prince M, Yamada K, Takayama S (1974) Diethylnitrosamine induced chromosome changes in rat liver cell. J Natl Cancer Inst 53:507–516
Inaoka Y (1967) Significance of the so-called oval cell proliferation during azodye hepatocarcinogenesis. Cancer 58:355–366
Kitagawa T, Sugano H (1973) Timetable for hepatocarcinogenesis in rat. Analytic and Experimental Epidemiology. University Tokyo Press, Tokyo, pp 91–105
Kitagawa T, Sugano H (1973) Combined enzyme histochemical and radioautographic studies on areas of hyperplasia in the liver of rat fed N-2-Fluorenylacetamide. Cancer Res 33:2993–3001
Kitamura O, Hidaka T, Ashihara T, Takeoka N, Okuda K, Takahashi S, Takino T (1979) Agerelated changes in ploidy classes of liver cells in human and rats as studied by Feulgen-DNA cytofluorometry. (Japanese with English Summary) Jpn J Gastroenterol 76:223–230
Leevy CM, Hollister RM, Schmid R, MacDonald RA, Davidson CS (1959): Liver regeneration in experimental CCl4 intoxication. Proc Soc Exp Biol Med 102:672–675
Merkow LP, Epstein SM, Farber E, Pardo M, Batus B (1969) Cellular analysis of liver carcinogenesis. III. Comparison of the ultrastructure of hyperplastic liver nodules and hepatocellular carcinomas induced in rat liver by 2-Fluorenylacetamide. J Natl Cancer Inst 43:33–64
Nagata T (1961) A quantative study of the DNA contents in rat hepatic cell nuclei by means of microspectrophotometry, with special reference to binucleate cells. Med J Shinshu Univ 6:143–153
Nagata T (1972) Application of microspectrophotometry to various substances. In: Isaka H (ed) Introduction to microspectrophotometry. Application to biomedical research. Olympus Optics Tokyo, pp 49–69
Nagata T, Shibata O, Nawa T (1967) Simplified methods for mass production of radioautographs. (Japanese with English Summary). Acta Anat Nipponica 42:162–166
Newberne PM, Wogam GN (1968) Sequential morphologic changes in aflatoxin B1 carcinogenesis in the rat. Cancer Res 28:770–781
Price JM, Harman JW, Miller EC, Miller JA (1952) Progressive microscopic alterations in the livers of rats fed the hepatic carcinogens 3′-methyl-4-dimethyl-aminoazobenzene and 4′-fluoro-4-dimethylaminoazobenzene. Cancer Res 12:192–220
Rueber MD (1965) Development of preneoplastic and neoplastic lesions of the liver in male rats given 0.025 pereent N-2-Fluorenyldiacetamide. J Natl Cancer Inst 34:697–724
Takehara K (1975) Studies on nucleic acid metabolism in diseased livers with special reference to different responses of each tissue constituent of the liver. (Japanese with English summary). Jpn J Gastroenterol 72:527–536
Takino T, Kitamura O, Kagawa K, Okuda K, Takahashi S, Masuda M, Hidaka K, Ashihara T, Takeoka N (1979) Analysis of ploidy classes of human liver cells in chronic active liver diseases as studied by Feulgen-DNA cytofluorometry. (Japanese with English summary). Acta Hepatol Jpn 20:377–387
Tamemasa O, Tezuka M, Fugisawa M, Takeda T (1978) Elevation of the salvage synthesis of ribonucleic acid in the rat liver during the induction of hepatoma with 3′-methyl-4-dimethyl-aminoazobenzene. Radioisotopes 27:509–519
Tokuoka J (1965): Studies on DNA content of malignant tumor cells. (Japanese). Jpn J Cancer Clin 11:133–141
Urachi M, Hidaka K, Kitamura O, Kanataka T, Takaoka N, Kagawa K, Takino T (1979) Polyploidization of human liver cells by administration of antimetabolites. (Japanese). Acta Hepatol Jpn 20:974
Yoshida T (1976): Nucleic acid metabolism in human chronic liver diseases by in vitro autoradiography. (Japanese with English summary). Jpn J Gastroenterol 73:627–637
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Koike, Y., Suzuki, Y., Nagata, A. et al. Studies on DNA content of hepatocytes in cirrhosis and hepatoma by means of microspectrophotometry and radioautography. Histochemistry 73, 549–562 (1982). https://doi.org/10.1007/BF00493368
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00493368