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The Effects of Heterologous Antithymocyte Sera in Mice

V. Enhancement of Plasma Cell Tumor Induction¹

From the Department of Surgery, University Hospitals of Cleveland and Case Western Reserve University School of Medicine, Cleveland, Ohio 44106

Abstract

The intraperitoneal inoculation of BALB/c mice with three doses of Bayol F resulted in the development of plasma cell tumors. Twelve months after the last Bayol dose 55% of mice had tumors. When mice were concomitantly treated with antithymocyte sera (ATS), tumors developed more rapidly and frequently than with Bayol alone. Suppression of host reactivity by other modalities, including the chemical agents, Imuran and Cytoxan, and by adult thymectomy, did not increase the rate of tumor induction. Irradiation of mice at the time of Bayol treatment resulted in a slightly higher incidence of tumor. Mice treated by suppressive therapy, without Bayol, did not develop tumors.

The enhanced rate of tumor induction noted with ATS and Bayol appears to be due, in great part, to selective destruction of lymphoid cells by the ATS with little direct effect on plasma cell elements. Treatment of mice with the chemical agents, however, did not enhance oncogenesis since these suppressed not only lymphoid cells but also malignant or potentially malignant plasma cells. In this experimental model, therefore, an increased rate of plasma cell tumor induction resulted when mice given Bayol were treated with ATS.

The effect of treatment with ATS on the type of tumor induced was studied by histologic methods and by analysis of ascitic fluid and serum for protein content. All induced tumors in each group were plasmacytomas, the majority of which synthesized IgA myeloma proteins. One-quarter of the mice developed tumors that synthesized IgG; IgM tumors were uncommon. Thus despite variations in the rate and intensity of oncogenesis for the different groups, the relative proportion of each myeloma class of induced tumor was constant.

Footnotes

¹ This study was supported by a grant from the Ohio Chapter of the American Cancer Society and from the Blywise Fund of University Hospitals of Cleveland.

² Advanced Clinical Fellow of the American Cancer Society.

³ Markle Scholar in Academic Medicine. Present address: Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin 53226.