Enhancing Potential of 6 Different Carcinogens on Multi‐organ Tumorigenesis after Initial Treatment with N‐Methyl‐N‐nitrosourea in Rats

The advantages of applying a whole‐body concept to the assessment of carcinogenic potential of compounds in a two‐stage model after initiation by N‐methyl‐N‐nitrosourea (MNU) were investigated. Male, 6‐week‐old F344 rats were injected with MNU (20 mg/kg, i. p.) twice a week for 4 weeks and they then received 3,2′‐dimethyl‐4‐aminobiphenyl (DMAB) (50 mg/kg, s.c., once a week), N,N′‐dibutylnitrosaraine (DBN) (0.05%, in drinking water), N‐bis(2‐hydroxypropyl)nitrosamine (DHPN) (0.1%, in drinking water), diethylstilbestrol (DES) (2.5 ppm, in diet), sodium o‐phenylphenate (S. OPP) (2%, in diet) or captafol (0.15%, in diet) for 20 weeks. All six carcinogens enhanced the incidences of preneoplastic and neoplastic lesions in their respective target organs: liver, pancreas, small intestine and urinary bladder with DMAB; liver, esophagus, forestomach and urinary bladder with DBN; thyroid, lung, liver, esophagus, forestomach, small intestine and urinary bladder with DHPN; liver and forestomach with DES; and thyroid, forestomach, kidney and urinary bladder with S. OPP; liver and forestomach with captafol. The results suggested that prior treatment with MNU sensitized the tissues to the organotropic carcinogenic potential of chemicals given thereafter for as short a period as 20 weeks. Thus, this system could be utilized as a whole‐body medium‐term bioassay system for the screening of environmental carcinogens, bridging the gap between in vitro mutagenicity and long‐term carcinogenicity tests.