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Effect of p-Hydroxyacetanilide, Sodium Sulfate, and L-Methionine on the Leukemogenicity of N-[4-(5-Nitro-2-furyl)-2-thiazolyl]acetamide¹

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

Dietary administration of N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide to mice for 14 weeks followed by 16 weeks of control diet resulted in a high incidence of lymphocytic leukemia and a low incidence of forestomach squamous cell papillomas. The coadministration of p-hydroxyacetanilide at a dose of 1.0% with either 250 or 500 ppm of N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide resulted in inhibition of leukemogenesis, whereas when p-hydroxyacetanilide was coadministered with 1000 ppm of N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide the leukemia incidence was not significantly reduced, but the latent period was prolonged. When sodium sulfate was administered with p-hydroxyacetanilide and N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide, leukemogenesis was partially restored. L-Methionine, fed in place of sodium sulfate, unblocked leukemogenicity inhibition by p-hydroxyacetanilide. None of these chemicals, p-hydroxyacetanilide, sodium sulfate, or L-methionine, significantly affected the incidence of forestomach papillomas induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]acetamide, although tumor incidences in all groups were low. p-Hydroxyacetanilide and sodium sulfate had no significant effect on the high incidence of stomach tumors induced by formic acid 2-[4-(5-nitro-2-furyl)-2-thiazolyl]hydrazide or bladder tumors induced by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.

¹ Supported in part by Grants CA-10017, CA-11946, and CA-14520 from the National Cancer Institute, USPHS. A preliminary report of this work was presented (8).

² Medical Scientist Trainee of National Institutes of General Medical Sciences, USPHS, Grant GM-01932. Submitted to the University of Wisconsin in partial fulfillment of the requirements for the Ph.D. degree. Present address: Department of Pathology, St. Vincent Hospital, Worcester, Mass. 01610.

Received 3/21/77. Accepted 2/ 9/78.