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Journal Article

Phenotypic Properties of Preneoplastic Rat Liver Lesions and Applications to Detection of Carcinogens and Tumor Promoters

Gary M. Williams, M.D.

Naylor Dana Institute for Disease Prevention

A variety of cellular lesions arise during liver carcinogenesis by chemicals in rats. The altered focus is a lesion of hepatocytes that occurs early in hepatocarcinogenesis and appears to give rise to both neoplastic nodules and carcinomas. Foci display numerous phenotypic abnormalities which together with nuclear abnormalities indicate that they are truly a new altered population.

Using histochemical markers, the induction of foci can be measured as a quantitative index of hepatocarcinogenicity of genotoxic carcinogens. In addition, determination of the effect of agents on foci previously induced by genotoxic carcinogens can be used to assess the capacity of chemicals to act as liver tumor promoters.

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  • 66. Williams GM and Weisburger JH: Systematic carcinogen testing through the decision point approach. Annu Rev Pharmacol Toxicol 21: 393–416, 1981.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 67. Ishkawa T, Takayama S, Kitagawa T, Kawachi T, Sugimura T: Induction of enzyme-altered islands in rat liver by tryptophan pyrolysis products. J Cancer Res Clin Oncol 95: 221–224, 1979.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 68. Laib RJ, Stöckle G, Bolt HM, Kunz W: Vinyl chloride and trichloroethylene: comparison of alkylating effects of metabolites and induction of preneoplastic enzyme deficiencies in rat liver. J Cancer Res Clin Oncol 94: 139–147, 1979.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 69. Bolt HM, Laib RJ, Stöckle G: Formation of pre-neoplastic hepatocellular foci by vinyl bromide in newborn rats. Arch Toxicol 43: 83–84, 1979.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • 70. Mazue G, Remandet B, Gouy D, Berthe J, Roncucci R, Williams GM: Limited in vivo bioassays on some benzodiazepines: Lack of experimental initiating or promoting effect of the benzodiazepine tranquilizers diazepam, clorazepate, oxazepam and lorazepam. Arch Int Pharmacodyn Ther 257: 59–65, 1982.[Web of Science][Medline] [Order article via Infotrieve]
  • 71. Peraino C, Staffeldt EF, Ludeman VA: Early appearance of histochemically altered hepatocyte foci and liver tumors in female rats treated with carcinogens one day after birth. Carcinogenesis 2: 463–465, 1981.[Abstract/Free Full Text]
  • 72. Tatematsu M, Shirai T, Tsuda H, Miyata Y, Shinohara Y, Ito N: Rapid production of hyperplastic liver nodules in rats treated with carcinogenic chemicals: A new approach for an in vivo short-term screening test for hepatocarcinogens. Gann 68: 499–507, 1977.[Web of Science][Medline] [Order article via Infotrieve]
  • 73. Tsuda H, Lee G, Farber E Induction of resistant hepatocytes as a new principle for a possible shortterm in vivo test for carcinogens. Cancer Res 40:1157–1164, 1980.[Abstract/Free Full Text]
  • 74. Mori H, Tanaka T, Nishikawa A, Takahashi M, Williams GM: Enhancing effect of barbital on N-2-fluorenylacetamide induced rat liver lesions. Gann 72: 798–801, 1981.[Web of Science][Medline] [Order article via Infotrieve]
  • 75. Pitot HC, Goldworthy T, Campbell HA, Poland A: Quantitative evaluation of the promotion by 2,3,7,8-tetrachlorodibenzo-p-dioxin of hepatocarcinogenesis from diethylnitrosamines. Cancer Res 40: 3616–3620, 1980.[Abstract/Free Full Text]
  • 76. Schulte-Hermann R, Ohde G, Schuppler J, Timmermann-Trosiener I: Enhanced proliferation of putative preneoplastic cells in rat liver following treatment with the tumor promoters phenobarbital, hexachlorocyclohexane, steroid compounds, and nafenopin. Cancer Res 41: 2556–2562, 1981.[Abstract/Free Full Text]
  • 77. Williams GM, Furuya K, Mori H: An enhancing effect of the antihistaminic drug methapyrilene on rat liver carcinogenesis by previously administered N-2-fluorenylacetamide. Toxicol App Pharmacol, in press.
  • 78. Williams GM, Katayama S, Ohmori T: Enhancement of hepatocarcinogenesis by sequential administration of chemicals: Summation versus promotion effects. Carcinogenesis 11: 1111–1117, 1981.
  • 79. Williams GM: Epigenetic effects of liver tumor promoters and implications for health effects. Environ Health Perspect, In press.

Toxicologic Pathology, Vol. 10, No. 2, 3-10 (1982)
DOI: 10.1177/019262338201000202
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