Induction of resistant hepatocytes as a new principle for a possible short-term in vivo test for carcinogens.

The induction of resistant hepatocytes in vivo in the rat has been observed with 21 different chemical carcinogens. The resistance was measured by the ability of the cells to proliferate as focal lesions in the presence of an environment that inhibits the original or surrounding hepatocytes from proliferation. This was created by a dietary 2-acetylaminofluorene plus a stimulus for cell proliferation, a single necrogenic dose of CCl4. The foci were readily visualized by staining for gamma-glutamyl transpeptidase activity. With most of the chemicals, a single administration at an appropriate time after partial hepatectomy is efficacious. However, with safrole and dieldrin, three doses over a 36-hr period were required to induce a significant number of foci of resistant hepatocytes. The presumptive preneoplastic nature of the resistant hepatocytes and the possible usefulness of this approach for the development of a new in vivo short-term test system for carcinogens are discussed.

[1]  W. Koransky,et al.  Hyperplasia and hypertrophy of rat liver induced by α-hexachlorcyclohexane and butylhydroxytoluene. Retention of the hyperplasia during involution of the enlarged organ , 1971, Virchows Archiv. B, Cell pathology.

[2]  Gary M Williams,et al.  Nature of Early Appearing, Carcinogen-Induced Liver Lesions Resistant to Iron Accumulation , 1976 .

[3]  V. Craddock.  Chapter 8 – CELL PROLIFERATION AND EXPERIMENTAL LIVER CANCER , 1976 .

[4]  H. Shinozuka,et al.  Enhancement of 2‐acetylaminofluorene liver carcinogenesis in rats fed a choline‐devoid diet , 1979, International journal of cancer.

[5]  A. Medline,et al.  Rapid emergence of carcinogen-induced hyperplastic lesions in a new model for the sequential analysis of liver carcinogenesis. , 1977, The American journal of pathology.

[6]  D. Martin,et al.  Liver response tests. V. Effect of dietary restriction on a short-term feeding study with butylated hydroxytoluene (BHT). , 1965, Food and cosmetics toxicology.

[7]  P. Emmelot,et al.  Kinetics of induction and growth of enzyme-deficient islands involved in hepatocarcinogenesis. , 1976, Cancer research.

[8]  E. Farber,et al.  The sequential analysis of cancer development. , 1980, Advances in cancer research.

[9]  M. Chiga,et al.  Initiation of the division cycle of rat hepatocytes following a single injection of thioacetamide. , 1969, Laboratory investigation; a journal of technical methods and pathology.

[10]  D. Judah,et al.  The effects of prolonged feeding with aflatoxin B1 on adult rat liver. , 1976, Cancer research.

[11]  W. H. Butler,et al.  Some effects of acute and chronic dosing with aflatoxin B1 on rat liver nuclei. , 1976, Cancer research.

[12]  D. Solt,et al.  New principle for the analysis of chemical carcinogenesis , 1976, Nature.

[13]  M. Kelly,et al.  Carcinogenicity of 1-methyl-1-nitrosourea in newborn mice and rats. , 1968, Journal of the National Cancer Institute.

[14]  D. Sarma,et al.  Initiation of chemical carcinogenesis requires cell proliferation , 1978, Nature.

[15]  M. Klein.  Development of hepatomas in inbred albino mice following treatment with 20-methylcholanthrene. , 1959, Cancer research.

[16]  B. Stewart,et al.  Strand breakage in rat liver DNA and its repair following administration of cyclic nitrosamines. , 1973, Cancer research.

[17]  D. Judah,et al.  Development of resistance to cytotoxicity during aflatoxin carcinogenesis , 1977, Nature.

[18]  R. Anderson,et al.  Experimental pathology of liver: restoration of liver in white rat following partial surgical removal , 1931 .