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American Journal of Pathology, Vol 110, 119-126, Copyright © 1983 by American Society for Investigative Pathology

REGULAR ARTICLES

An experimental method for rapid growth of liver in spleen. The survival and proliferation of chemically induced preneoplastic hepatocytes in spleen

SD Finkelstein, G Lee, A Medline, M Tatematsu, L Makowka and E Farber

Cellular suspensions (2 x 10(6) cells) of isolated preneoplastic liver cells, obtained from carcinogen-treated rats, were injected in the spleens of syngeneic rats divided into groups on the basis of no treatment, partial hepatectomy (PH), and/or feeding regimens including 2-acetylaminofluorene (AAF). Recipient rats undergoing both PH and AAF showed significantly more rapid proliferation of the preneoplastic liver cell implant, compared with other treatment groups and control. The theoretic basis for this observation, supported by a large body of data derived from hepatocarcinogenesis, is as follows: The phenotype of the donor cells has been altered by chemical carcinogens such that the liver cells develop resistance to growth-inhibiting agents such as AAF. The recipient receives PH and AAF, the former creating a strong proliferative stimulus for hepatocytes, while the latter inhibits regeneration of normal liver cells but not those resistant to the mito- inhibitory effect of AAF, ie, the carcinogen-altered donor cells. These manipulations in donors and recipients thus create a selective environment in which the implant undergoes rapid proliferation. This model of resistance induction followed by selective proliferation, built upon the principles of carcinogenesis and applied to isolated liver cell transplantation, provides an experimental basis for achieving rapid liver growth of the splenic implant.




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Copyright © 1983 by the American Society for Investigative Pathology.