© 1991 Oxford University Press
research-article |
Synergistic enhancement of thyroid tumor induction by 2,4-diaminoanisole sulfate, N,N'-diethylthiourea and 4,4'-thiodianiline in male F344 rats
First Department of Pathology, Nagoya City University Medical School 1-Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467, Japan
1Growth Factor Division, National Cancer Center Research Institute 5-1-1 Tsukiji, Chuo-ku, Tokyo 104, Japan
2National Cancer Center Research Institute 5-1-1 Tsukiji, Chuo-ku, Tokyo 104, Japan
Three thyroid carcinogens, 2,4-diaminoanisole sulfate (DAAS), N,N'-diethylthiourea (DETU) and 4,4'-thiodianiline (IDA), were simultaneously administered in the diet to male K344 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.