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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1996 Feb;87(2):122–126. doi: 10.1111/j.1349-7006.1996.tb03148.x

Chemopreventive Effects of 3‐Phenylpropyl Isothiocyanate on Hamster Lung Tumorigenesis Initiated with N‐Nitrosobis(2‐oxopropyl)amine

Akiyoshi Nishikawa 1,✉, Fumio Furukawa 1, Shinichiro Ikezaki 1, Zen‐yo Tanakamaru 1, Fung‐Lung Chung 2, Michihito Takahashi 1, Yuzo Hayashi 1
PMCID: PMC5921064  PMID: 8609059

Abstract

The chemopreventive effects of 3‐phenylpropyl isothiocyanate (PPITC) were investigated in N‐nitrosobis(2‐oxopropyl)amine (BOP)‐initiated hamsters. A total of 120 female 5‐week‐old hamsters were divided into 6 groups. Animals in groups 1–3, each consisting of 30 hamsters, were twice sc injected 7 days apart as an initiation treatment. Hamsters in groups 1 and 2 were respectively given 100 μmol and 10 μmol of PPITC by gavage 2 h prior to each BOP treatment. Animals in group 3 were treated with BOP alone, serving as an initiation‐positive control. Animals in groups 4–6, each consisting of 10 hamsters, were given 100 μmol or 10 μmol of PPITC alone, or non‐treated, thus being available as matched negative controls to groups 1–3. At termination (experimental week 51 after the first BOP injection), the incidences of lung adenomas and/or adenocarcinomas were significantly decreased in groups 1 and 2 as compared to the group 3 value (P<0.01). The combined lung tumor incidences were inhibited by 94% and 59% at 100 and 10 μmol doses, respectively. The inhibitory effects of PPITC were thus dose‐dependent. The data for multiplicity of lung tumors dramatically illustrated the inhibitory effects of PPITC, and there were also statistically significant differences in the chemopreventive effect between 100 μmol and 10 μmol PPITC treatments. On the other hand, the PPITC treatments did not significantly modulate the development of neoplastic lesions in the pancreas, liver and kidney, although the treatments did show inhibitory tendencies, except on the liver lesions. Under the present experimental conditions, PPITC itself did not exhibit tumorigenicity or apparent toxicity. The results in the present study thus clearly indicate that PPITC has an effective chemopreventive action on BOP‐induced lung tumorigenesis in hamsters.

Keywords: PPITC, Chemoprevention, Lung, BOP, Hamster

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REFERENCES

  • 1).Daxenbichler , M. E. , Spencer , G. F. , Carlson , D. G. , Rose , G. B. , Brinker , A. B. and Powell , R. G.Glucosinolate composition of seeds from 297 species of wild plants . Phytochemistry 30 , 2623 – 2638 ( 1991. ). [Google Scholar]
  • 2).Morse , M. A. , Wang , C.‐X. , Stoner , G. D. , Mandal , S. , Conran , P. B. , Amin , S. G. , Hecht , S. S. and Chung , F.‐L.Inhibition of 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone‐induced DNA adduct formation and tumorigenicity in the lung of F344 rats by dietary phenethyl isothiocyanate . Cancer Res. 49 , 549 – 553 ( 1989. ). [PubMed] [Google Scholar]
  • 3).Morse , M. A. , Amin , S. G. , Hecht , S. S. and Chung , F.‐L.Effects of aromatic isothiocyanates on tumorigenicity, O6‐methylguanine formation, and metabolism of the tobacco‐specific nitrosamine 4‐(methylnitrosamino)‐l‐(3‐pyridyl)‐l‐butanone in A/J mouse lung . Cancer Res. 49 , 2894 – 2897 ( 1989. ). [PubMed] [Google Scholar]
  • 4).Morse , M. A. , Eklind , K. I. , Amin , S. G. , Hecht , S. S. and Chung , F.‐L.Effects of alkyl chain length on the inhibition of NNK‐induced lung neoplasia in A/J mice by arylalkyl isothiocyanates . Carcinogenesis 10 , 1757 – 1759 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 5).Morse , M. A. , Eklind , K. I. , Hecht , S. S. , Jordan , K. G. , Choi , C.‐I. , Desai , D. H. , Amin , S. G. and Chung , F.‐L.Structure‐activity relationship for inhibition of 4‐(methylnitrosamino) ‐1 ‐(3 ‐pyridyl)‐1 ‐butanone lung tumorigenesis by arylalkyl isothiocyanates in A/J mice . Cancer Res. 51 , 1846 – 1850 ( 1991. ). [PubMed] [Google Scholar]
  • 6).Jiao , D. , Eklind , K. I. , Choi , C.‐I. , Desai , D. H. , Amin , S. G. and Chung , F.‐L.Structure‐activity relationships of isothiocyanates as mechanism‐based inhibitors of 4‐ (methylnitrosamino) ‐1 ‐ (3‐pyridyl) ‐1 ‐butanone‐induced lung tumorigenesis in A/J mice . Cancer Res. 54 , 4327 – 4333 ( 1994. ). [PubMed] [Google Scholar]
  • 7).Wattenberg , L. W.Inhibition of carcinogenic effects of polycyclic hydrocarbons by benzyl isothiocyanate and related compounds . J. Natl. Cancer Inst. 58 , 395 – 398 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 8).Stoner , G. D. , Morrissey , D. T. , Heur , Y.‐H. , Daniel , E. M. , Galati , A. J. and Wagner , S. A.Inhibitory effects of phenethyl isothiocyanate on N‐nitrosobenzylmethyl‐amine carcinogenesis in the rat esophagus . Cancer Res. 51 , 2063 – 2068 ( 1991. ). [PubMed] [Google Scholar]
  • 9).Morse , M. A. , Zu , H. , Galati , A. J. , Schmidt , C. J. and Stoner , G. D.Dose‐related inhibition by dietary phenethyl isothiocyanate of esophageal tumorigenesis and DNA methylation induced by N‐nitrosomethylbenzylamine in rats . Cancer Lett. 72 , 103 – 110 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 10).Pour , P. M. , Althoff , J. , Krüger , F. W. and Mohr , U.A potent pancreatic carcinogen in Syrian hamsters: N‐nitrosobis(2‐oxopropyl)amine . J. Natl. Cancer Inst. 58 , 1449 – 1453 ( 1977. ). [DOI] [PubMed] [Google Scholar]
  • 11).Hoffmann , D. , Rivenson , A. , Hecht , S. S. , Hilfrich , J. , Kobayashi , N. and Wynder , E. L.Model studies in tobacco carcinogenesis with the Syrian golden hamster . In “ The Syrian Hamster in Toxicology and Carcinogenesis Research ,” ed. Homburger F. , Progress in Experimental Tumor Research Vol. 24 , pp . 370 – 390 ( 1979. ). Karger; , Basel . [DOI] [PubMed] [Google Scholar]
  • 12).Takahashi , M. , Furukawa , F. , Toyoda , K. , Sato , H. , Hasegawa , R. , Imaida , K. and Hayashi , Y.Effects of various prostaglandin synthesis inhibitors on pancreatic carcinogenesis in hamsters after initiation with N‐nitrosobis(2‐oxopropyl)amine . Carcinogenesis 11 , 393 – 395 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 13).Guo , Z. , Smith , T. J. , Wang , E. , Sadrieh , N. , Ma , Q. , Thomas , P. E. and Yang , C. S.Effects of phenethyl isothiocyanate, a carcinogenesis inhibitor, on xenobioticmetabolizing enzymes and nitrosamine metabolism in rats . Carcinogenesis 13 , 2205 – 2210 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 14).Guo , Z. , Smith , T. J. , Wang , E. , Eklind , K. L. , Chung , F.‐L. and Yang , C. S.Structure‐activity relationship of arylalkyl isothiocyanates for the inhibition of 4‐(methylnitrosamino) ‐1‐(3 ‐pyridyl)‐1‐butanone metabolism and the modulation of xenobiotic‐metabolizing enzymes in rats and mice . Carcinogenesis 14 , 1167 – 1173 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 15).Smith , T. J. , Guo , Z. , Li , C. , Ning , S. M. , Thomas , P. E. and Yang , C. S.Mechanisms of inhibition of 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanone bioactiva tion in mouse by dietary phenethyl isothiocyanate . Cancer Res. 53 , 3276 – 3282 ( 1993. ). [PubMed] [Google Scholar]
  • 16).Yang , C. S. , Smith , T. J. and Hong , J.‐Y.Cytochrome P‐450 enzymes as targets for chemoprevention against chemical carcinogenesis and toxicity: opportunities and limitations . Cancer Res. , 54 ( Suppl. ), 1982s – 1986s ( 1994. ). [PubMed] [Google Scholar]
  • 17).Hamilton , S. M. , Zhang , Z. and Teel , R. W.Effects of isothiocyanate alkyl chain‐length on hamster liver cyto chrome P‐450 activity . Cancer Lett. 82 , 217 – 224 ( 1994. ). [DOI] [PubMed] [Google Scholar]

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