This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Kroes, R. Articles by Weisburger, J. H. Search for Related Content PubMed PubMed Citation Articles by Kroes, R. Articles by Weisburger, J. H.

Immunosuppression in Primary Liver and Colon Tumor Induction with N-Hydroxy-N-2-fluorenylacetamide and Azoxymethane

National Institute of Public Health, Bilthoven, Netherlands [R. K., J. M. B.]; National Cancer Institute, Bethesda, Maryland 20014 [R. K., J. H. W.]; and American Health Foundation, Valhalla, New York 10595 [J. H. W.]

The question was examined as to whether immunosuppression in a rat model system would affect the carcinogenic processes leading to tumors in the liver and the large bowel. The protocols were designed to detect an increased incidence or a shorter latent period stemming from a change in immune status.

Groups of rats were given injections prior to initiation of the carcinogen regimen and continuously thereafter with a purified fraction of antilymphocytic serum (ALG). Appropriate controls received the fraction of normal rabbit serum, or 0.9% NaCl solution. Permanence of skin allografts showed that ALG was an effective immunosuppressive treatment. For liver cancer induction, rats were fed 120 ppm N-hydroxy-N-2-fluorenylacetamide in the diet for 16 weeks, then were continued on control diet. The animals given ALG developed liver tumors at a rate similar to that of controls.

For cancer of the large bowel, rats received a single s.c. dose of 7.5 mg azoxymethane per kg per week for 16 weeks and were then held on control diet. With an identical ALG treatment, there were fewer intestinal tumors in the early part of the treatment, because of the important early development of liver angiosarcoma, not seen in control rats given injections of 0.9% NaCl solution. At a later time, the incidence of intestinal cancer was similar in rats on ALG or on 0.9% NaCl solution.

Thus, immunosuppression had little effect on the rate of liver tumor formation with a liver carcinogen. Also, ALG led to the precocious development of liver angiosarcomas, but failed to affect intestinal cancer induction in animals given azoxymethane.

¹ This work was undertaken at the National Cancer Institute during a tenure of Research Training Fellowship (awarded by the International Agency for Research on Cancer, Lyon, France), while the recipient was on leave of absence from the Laboratory of Pathology, Rijksinstituut voor de Volksgezondheid, Bilthoven, Netherlands (his present address).

² Research assistant, Rijksinstituut voor de Volksgezondheid, Bilthoven, Netherlands.

³ Supported in part by Grants CA-12376, CA-14298, CA-15400, CA-17613, and Contract CP-33208 from the National Cancer Institute, NIH, USPHS. Present address: Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, N. Y. 10595. To whom reprint requests should be addressed.

Received 11/21/74. Accepted 6/12/75.