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Sequential Morphologic Changes in Aflatoxin B₁ Carcinogenesis in the Rat^{1 ,2}

Department of Nutrition and Food Science, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Highly purified aflatoxin B₁ was administered for long periods of time and in different concentrations to both male and female Fischer-strain rats. The development of liver cell carcinoma followed a pattern of sequential histologic changes, the chronology of which depended upon both sex and dose level. The patterns of change in the liver were of 2 types: focal hyperplasia of basophilic-staining parenchymal cells seen within a few weeks after initiation of the experiment, or foci of large, pale eosinophilic cells observed slightly later. In both types, the initial changes were followed by nodule formation, hepatoma, and, ultimately, liver cell carcinoma; the degree of differentiation varied with the earlier pattern. There was a high incidence of tumor development in rats of both sexes continuously fed a level of aflatoxin as low as 0.015 ppm for 68–80 weeks; the females required the longer period of time before tumors were observed. Liver tumors caused by other hepatic carcinogens are compared with those induced by aflatoxin.

¹ This study was supported by Contract No. PH 43-62-468 with the National Cancer Institute, NIH, USPHS.

² This manuscript is Contribution No. 1104 from the Department of Nutrition and Food Science, Massachusetts Institute of Technology.

Received 7/24/67. Accepted 12/31/67.

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