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Changes in Peroxisomes in Preneoplastic Liver of Rats Induced by 3'-Methyl-4-dimethylaminoazobenzene¹

Department of Pathology, Cancer Research Institute, Sapporo Medical College, S-1, W-17, Chuo-ku, Sapporo 060, Japan

Histochemical investigations used the 3,3'-diaminobenzidine reaction to demonstrate the catalase activity and thus variations in numbers of peroxisomes, and electron microscopic examinations were made of hyperplastic liver lesions in rats fed 0.06% 3'-methyl-4-dimethylaminoazobenzene. At the 10th week of carcinogen feeding, hyperplastic lesions (hyperplastic foci, areas, and nodules) appeared and advanced to further stages. Most of the foci and some of the areas and nodules showed very low catalase activity and, correspondingly, a small number of peroxisomes. When rats were administered ethyl--p-chlorophenoxyisobutyrate, most of the foci, areas, and nodules showed a moderate increase in catalase activity and in peroxisome number. Hyperplastic foci seemed to grow larger with time to form hyperplastic areas and/or nodules, mostly accompanying maturation as well as proliferation of the hepatocytes involved. Maturation is well characterized by an increase in the endogenous level of catalase and in the number of peroxisomes, as well as by an enhancement of the responsiveness to ethyl--p-chlorophenoxyisobutyrate. However, there was a small proportion of lesions in which all cells or some cells did not mature and thus were considered persistently altered. It is suggested that these altered cells serve mainly as intimate precursors of hepatomas.

¹ Supported in part by Grants-in-aid for Cancer Research 001052 and 001055 from the Ministry of Education, Science and Culture, Japan.

² Present address: National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104, Japan.

³ To whom requests for reprints should be addressed.

Received 10/ 1/76. Accepted 12/10/76.