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Suppression of Antibody-mediated and Cell-mediated Murine Immunity by the Carcinogen N-[4-(5-Nitro-2-furyl)-2-thiazolyl]acetamide¹

Department of Human Oncology, University of Wisconsin Center for Health Sciences, Madison, Wisconsin 53706

N-[4-(5-Nitro-2-furyl)-2-thiazolyl]acetamide (NFTA) administered at 1000 ppm in diet to mice for 12 weeks induced a high incidence of lymphocytic leukemia. Effects of NFTA on antibody-mediated immunity and cell-mediated immunity of BALB/c mice were studied using the spleen plaque assay for detection of immunoglobulin M-producing cells and the graft-versus-host (GVH) reaction, respectively. NFTA suppressed both responses. With the spleen plaque assay, the number of antibody-forming cells (AFC) to sheep red blood cells was significantly less than in unmedicated, control mice after treated mice received NFTA at 1000 ppm for 6 days. The GVH reaction was not suppressed at 21 days, but was severely suppressed at 70 days, prior to the histological appearance of leukemia. Effect of dose was studied by administering NFTA at 100, 250, 500, and 1000 ppm of diet for 13 to 14 weeks and then determining the response in the spleen plaque assay and GVH reactions. The ratio of AFC/spleen of NFTA-treated groups to AFC/spleen of an unmedicated control group, at the above specified doses, was 0.86, 0.22, 0.33, and 0.54 in ascending dosage order beginning with 100 ppm. For the GVH reaction, the suppression of the cell-mediated immunity was directly proportional to the dose of NFTA. Suppression of the antibody-mediated immunity in relation to the induction of leukemia at 28 weeks was studied by feeding NFTA at 500 ppm for 14 weeks, followed by unmedicated diet for 14 weeks. During the 11th week, mice were immunized with SRBC; 5 days later the spleens were removed and the spleen plaque assay was performed. Eight of 18 mice fed NFTA developed leukemia. The number of AFC/spleen was 78 x 10³ ± 34 for those with leukemia and 68 x 10³ ± 24 (p > 0.5) for those without leukemia, compared with 170 x 10³ ± 74 for the control mice (p < 0.01 for both groups, compared with controls). A closely related carcinogenic nitrofuran, N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide, did not suppress the antibody-mediated immunity response measured during the 11th week of administration.

¹ Supported in part by Grants CA 10017, CA 11946, and CA 14520 from the National Cancer Institute, USPHS. Preliminary reports of this work have been made (9, 19).

² Present address: 5 Woodford Street, Worcester, Mass. 01604.

³ To whom requests for reprints should be addressed, at Department of Human Oncology, University of Wisconsin Center for Health Sciences, 1300 University Avenue, Madison, Wis. 53706.

Received 8/ 2/76. Accepted 12/20/76.