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), N,N'-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.
Hasegawa
R
R
First Department of Pathology, Nagoya City University Medical School, Japan.
Shirai
T
T
Hakoi
K
K
Wada
S
S
Yamaguchi
K
K
Takayama
S
S
D000814:Aniline Compounds / Q000633:toxicity*; D000818:Animals; D004357:Drug Synergism; D008297:Male; D010655:Phenylenediamines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D013890:Thiourea / Q000031:analogs & derivatives* / Q000633:toxicity; D013964:Thyroid Neoplasms / Q000139:chemically induced* / Q000473:pathology
D000814:Aniline Compounds; D010655:Phenylenediamines; C035318:diethylthiourea; C011749:4,4'-thiodianiline; C007294:4-methoxy-3-phenylenediamine; D013890:Thiourea