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Hyperlipidemia Enhancement of Renal Preneoplasia but not Tumor Formation Is Due to Elevated Apoptosis in the Eker Rat¹

Nissei Hospital, 6-3-8 Itachibori, Nishi-ku, Osaka 550 [S. M., B. S., M. Y.]; Miki Clinic, 2-2-1 Kuzuhara, Neyagawa-shi, Osaka 572 [Y. M.]; and Department of Experimental Pathology, Cancer Institute, 1-37-I Kami-ikebukuro, Toshima-ku, Tokyo 170 [H. M., O. H.], Japan

The influence of a high-fat diet on the appearance of renal tumors was assessed in the Eker rat model of hereditary renal carcinoma. Examination of H&E-stained sections showed a significant increase in the number of microscopic solid adenomas in the high-fat group compared with the low-fat group, whereas there was no significant difference in the number of macroscopic tumors between the two groups. Where had the tumor buds gone? Staining for apoptotic bodies occasionally revealed apoptosis in and around the microscopic adenomas. In addition, an Eker rat renal tumor-derived cell line showed apoptosis when it was cultured with high concentrations of native and acetylated low-density lipoprotein. These findings suggested that tumor buds repeatedly appeared and disappeared in Eker rats on a high-fat diet.

¹ This work was supported in part by a Grant-in-Aid for Cancer Research from the Ministry of Education, Science, Sports and Culture of Japan and the Council for Tobacco Research (United States).

² The first two authors contributed equally to this work and are both considered primary authors.

³ To whom requests for reprints should be addressed. Fax: 81-720-38-6568; E-mail: mikiy@po.aianet.or.jp.

Received 7/30/97. Accepted 9/22/97.