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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1991 Dec;82(12):1397–1405. doi: 10.1111/j.1349-7006.1991.tb01812.x

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

Satoshi Uwagawa 1, Hiroyuki Tsuda 1,†, Tadashi Inoue 1, Yoshiaki Tagawa 1, Toyohiko Aoki 1, Masataka Kagawa 1, Tadashi Ogiso 1, Nobuyuki Ito 1
PMCID: PMC5918354  PMID: 1778764

Abstract

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.

Keywords: Multi‐organ tumorigenesis, Rat, N‐Methyl‐N‐nitrosourea, Neoplastic lesion development

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