SYNERGISTIC ENHANCEMENT OF THYROID-TUMOR INDUCTION BY 2,4-DIAMINOANISOLE SULFATE, N,N'-DIETHYLTHIOUREA AND 4,4'-THIODIANILINE IN MALE F344 RATS

Three thyroid carcinogens, 2,4-diaminoanisole sulfate (DAAS), NN'-diethylthiourea (DETU) and 4,4'-thiodianiline (TDA), were simultaneously administered in the diet to male F344 rats at one-third the concentration of the reported TD50 levels (610, 200 and 46 p.p.m. respectively) for 52 weeks. The resultant incidence of thyroid adenocarcinomas in the combined treatment group (18/18: 100%) was significantly higher than those in each individual treatment group (DAAS, 0/21; DETU, 1/21; TDA, 2/20). Hepatocellular carcinomas (9/18, 50%) and lung adenomas (6/18, 33%) were also induced by the combined treatment, the incidences being higher than in the TDA group (3/20, 15% and 4/20, 20% respectively) to which these tumors- were limited in the three groups treated with single chemicals. Thus, the results indicated that the three carcinogens exert apparent synergism in thyroid carcinogenesis when administered simultaneously.