Abstract
Two wide‐spectrum initiation models were investigated in F344 male rats. Model I: After sequential treatment with diethylnitrosamine (DEN), N‐methylnitrosourea (MNU) and dihydroxy‐di‐N‐propylnitrosamine (DHPN), animals were given phenobarbital (PB) or N, N‐dibutylnitrosamine (DBN) as a test compound for 14 weeks and sacrificed at week 18. Model II: Animals were treated with DHPN, followed by N‐ethyl‐N‐hydroxyethylnitrosamine (EHEN), and then 3,2′‐dimethyl‐4‐aminobiphenyl (DMAB) as initiators and were subsequently given 3‐methylcholanthrene (MCA) or PB as a test compound for 11 weeks. Animals were sacrificed 16 weeks after the commencement. In both models, assessment of lesion yield revealed significant enhancement of carcinogenesis by the test compounds in their respective target organs. Since, in many cases, treatment with PB, DBN and MCA subsequent to the combined initiation procedures brought about a marked increase in lesion development, far greater than a simple sum of the yields given by initiators and test compounds alone, the presently described approach appears promising for development of medium‐term bioassay systems for detection of environmental carcinogens.
Keywords: Multiple organs, Bioassay system, Carcinogens, Promoters, Neoplastic change, Rat
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References
- 1. ) Ito , N. , Tsuda , H. , Hasegawa , R. and Imaida , K.Comparison of the promoting effects of various agents in induction of preneoplastic lesions in rat liver . Environ. Health Perspect. 50 , 131 – 138 ( 1983. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2. ) Bannasch , P. , Griesemer , R. A. , Anders , F. , Becker , R. , Cabral , J. R. , Della Porta , G. , Feron , V. J. , Henschler , D. , Ito , N. , Kroes , R. , Magee , P. N. , McKnight , B. , Mohr , U. , Montesano , R. , Napalkov , N. P. , Nesnow , S. , Roberfroid , M. , Slaga , T. , Turusov , Wilbourn J. , and Williams , G. M.Assays for initiating and promoting activities . In “ Long‐term and Short‐term Assays for Carcinogens: A Critical Appraisal ,” ed. Montesano R. , Bartsch H. , Vainio H. , Wilbourn J. and Yamasaki H. , IARC Scientific Publications No. 83 , pp. 103 – 126 ( 1986. ). Oxford University Press; , London . [PubMed] [Google Scholar]
- 3. ) Fukushima , S. , Hagiwara , A. , Ogiso , T. , Shibata , M. and Ito , N.Promoting effects of various chemicals in rat urinary bladder carcinogenesis initiated by N‐nitroso‐N‐butyl‐(4‐hydroxybutyl)amine . Food Chem. Toxicol. 21 , 59 – 68 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Tatematsu , M. , Furihata , C. , Katsuyama , T. , Mera , Y. , Inoue , T. , Matsushima , T. and Ito , N.Immunohistochemical demonstration of pyloric gland‐type cells with low‐pepsinogen isozyme 1 in preneoplastic and neoplastic tissues of rat stomachs treated with N‐methy1‐N'‐nitro‐N‐nitrosoguanidine . J. Natl. Cancer Inst. 78 , 771 – 777 ( 1987. ). [PubMed] [Google Scholar]
- 5. ) Sato , K. , Kitahara , A. , Satoh , K. , Ishikawa , T. , Tatematsu , M. and Ito , N.The placental form of glutathione S‐transferase as a new marker protein for preneoplasia in rat chemical hepatocarcinogenesis . Gann 75 , 199 – 202 ( 1984. ). [PubMed] [Google Scholar]
- 6. ) Satoh , K. , Kitahara , A. , Soma , Y. , Inaba , Y. , Hatayama , I. and Sato , K.Purification, induction, and distribution of placental glutathione transferase: a new marker enzyme for preneoplastic cells in the rat chemical carcinogenesis . Proc. Natl. Acad. Sci. USA 82 , 3964 – 3968 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7. ) Ito , N. , Tsuda , H. , Tatematsu , M. , Inoue , T. , Tagawa , Y. , Aoki , T. , Uwagawa , S. , Ogiso , T. , Masui , T. , Imaida , K. , Fukushima , S. and Asamoto , M.Enhancing effect of various hepatocarcinogens on induction of preneoplastic glutathione S‐transferase‐P form positive foci in rats — an approach for a new medium‐term bioassay system . Carcinogenesis 9 , 387 – 394 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Kitagawa , T. and Sugano , H.Enhancing effect of phenobarbital on the development of enzyme‐altered islands and hepatocellular carcinomas initiated by 3′‐methyl‐4‐(di‐methylamino)azobenzene or diethylnitrosamine . Gann 69 , 679 – 687 ( 1978. ). [PubMed] [Google Scholar]
- 9. ) Tsuda , H. , Fukushima , S. , Imaida , K. , Kurata , Y. and Ito , N.Organ‐specific promoting effect of phenobarbital and saccharin in induction of thyroid, liver, and urinary bladder tumors in rats after initiation with N‐methylnitrosourea . Cancer Res. 43 , 3292 – 3296 ( 1983. ). [PubMed] [Google Scholar]
- 10. ) Imaida , K. and Wang , C. Y.Effect of sodium phenobarbital and sodium saccharin in AIN‐76A diet on carcinogenesis initiated with N‐[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl]‐formamide and N,N‐dibutylnitrosamine in male F344 rats . Cancer Res. 46 , 6160 – 6164 ( 1986. ). [PubMed] [Google Scholar]
- 11. ) Druckrey , H. , Preussmann , R. , Ivankovic , S. , Schmidt , C. H. , Mennel , H. D. and Stahl , K. W.Selektive Erzeugung von Blasenkrebs an Ratten durch Dibutyl‐ und N‐Butyl‐N‐butanol(4)‐nitrosamine . Z. Krebsforsch. 66 , 280 – 290 ( 1964. ). [PubMed] [Google Scholar]
- 12. ) Pitot , H. , Barsness , L. , Goldsworthy , T. and Kitagawa , T.Biochemical characterization of stages of hepatocarcinogenesis after a single dose of diethylnitrosamine . Nature 271 , 456 – 458 ( 1978. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Tatematsu , M. , Nakanishi , K. , Murasaki , G. , Miyata , Y. , Hirose , M. and Ito , N.Enhancing effect of inducers of liver microsomal enzymes on induction of hyperplastic liver nodules by N‐2‐fluorenylacetamide in rats . J. Natl. Cancer Inst. 63 , 1411 – 1416 ( 1979. ). [PubMed] [Google Scholar]