title: Enhancing potential of 6 different carcinogens on multi-organ tumorigenesis after initial treatment with N-methyl-N-nitrosourea in rats.
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'-dibutylnitrosamine (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.
authors.affiliation: First Department of Pathology, Nagoya City University Medical School.
authors.forename: S
authors.initials: S
authors.lastname: Uwagawa
authors.forename: H
authors.initials: H
authors.lastname: Tsuda
authors.forename: T
authors.initials: T
authors.lastname: Inoue
authors.forename: Y
authors.initials: Y
authors.lastname: Tagawa
authors.forename: T
authors.initials: T
authors.lastname: Aoki
authors.forename: M
authors.initials: M
authors.lastname: Kagawa
authors.forename: T
authors.initials: T
authors.lastname: Ogiso
authors.forename: N
authors.initials: N
authors.lastname: Ito
mesh_terms: D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods; D002273:Carcinogens; D004357:Drug Synergism; D008297:Male; D008770:Methylnitrosourea; D009374:Neoplasms, Experimental / Q000139:chemically induced*; D009928:Organ Specificity; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D002273:Carcinogens; D008770:Methylnitrosourea