Summary
The modifying effects of indole-3-carbinol (I3C), a naturally occurring compound in cruciferous vegetables, were assessed using a rat multiorgan carcinogenesis model. One hundred male Sprague-Dawley (SD) rats were divided randomly into three groups. Groups 1 and 2 were sequentially treated with diethylnitrosamine (DEN), N-methyl-N-nitrosourea (MNU), and dihydroxy-di-N-propylnitrosamine (DHPN) for four weeks (DMD treatment) and Group 3 was given treatment without mutagen. Animals of groups 1 and 3 were given a diet containing 0.25% I3C for 20 weeks after the initiation period, followed by a return to the basal diet for 28 weeks, and subgroups were killed at weeks 24 and 52. I3C caused significant increases in both density and area (mm2/ cm2) of liver cell foci positive for glutathione S-transferase placental form, assessed at week 24 of the experiment (P < 0.01, 0.001). The incidence of hepatocellular adenomas in the DMD → I3C group at week 52 similarly tended to be elevated as compared to the initiation only (DMD-alone) group. The incidence of thyroid gland tumors in the DMD → I3C group was significantly increased compared with the DMD-alone group values at week 52 of the experiment (P < 0.01). In conclusion, I3C was shown to enhance liver and thyroid gland neoplastic development when given during the promotion stage in a rat medium-term multiorgan carcinogenesis model.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Hayatsu H, Arimoto S, Negishi T (1988) Dietary inhibitors of mutagenesis and carcinogenesis. Mutat Res 202:429–446
Wattenberg LW (1990) Inhibition of carcinogenesis by naturally occurring and synthetic compounds. In: Kurada Y, Shankel DM, Waters MD (eds) Antimutagenesis and anticarcinogenesis mechanisms II. Plenum, New York, pp 155–166
Williams DE, Dashwood RH, Hendricks JD, Bailey GS (1990) Anticarcinogens and tumor promoters in foods. In: Taylor SL, Scanlan RA (eds) Food toxicology—a perspective on the relative risks. Marcel Dekker, New York, pp 101–150
Loub WD, Wattenberg LW, Davis DW (1975) Aryl hydrocarbon hydroxylase induction in rat tissues by naturally occurring indoles of cruciferous plants. J Natl Cancer Inst 54:985–988
McDanell R, McLean AEM, Hanley AB, Heaney RK, Fenwick GR (1988) Chemical and biological properties of indole glucosinolates (Glucobrassicins): a review. Food Chem Toxicol 26:59–70
Kim DJ, Lee KK, Bae JH, Jang JJ, Tatematsu M, Furihata C (1994) The inhibitory effects of allyl sulfide and indole-3-carbinol on N-methyl-N′-nitro-N-nitrosoguanidine-induced glandular stomach carcinogenesis in rats. J Korean Cancer Assoc 26:392–398
Bradlow HL, Michnovicz JJ, Telang NT, Osborne MP(1991) Effects of dietary indole-3-carbinol on estradiol metabolism and spontaneous mammary tumors in mice. Carcinogenesis 12:1571–1574
Kojima T, Tanaka T, Mori H (1994) Chemoprevention of spontaneous endometrial cancer in female Donryu rats by dietary indole-3-carbinol. Cancer Res 54:1446–1448
Tanaka T, Kojima T, Morishita Y, Mori H (1992) Inhibitory effects of the natural products indole-3-carbinol and sinigrin during initiation and promotion phases of 4-nitroquinoline 1-oxide-induced rat tongue carcinogenesis. Jpn J Cancer Res 83:835–842
Tanaka T, Mori Y, Morishita Y, Hara A, Ohno T, Kojima T, Mori H (1990) Inhibitory effect of sinigrin and indole-3-carbinol on diethylnitrosamine-induced hepatocarcinogenesis in male ACI/N rats. Carcinogenesis 11:1403–1406
Kim DJ, Lee KK, Ahn B, Han BS, Bae JH, Jang JJ (1994) Biphasic modifying effect of indole-3-carbinol on diethylnitrosamine-induced preneoplastic glutathione S-transferase placental form positive liver cell foci in Sprague-Dawley rats. Jpn J Cancer Res 85:578–583
Nixon JE, Hendricks JD, Pawlowski NE, Pereira CB, Sinnhuber RO, Bailey GS (1984) Inhibition of aflatoxin B, carcinogenesis in rainbow trout by flavone and indole compounds. Carcinogenesis 5:615–619
Bailey GS, Hendricks JD, Shelton DW, Nixon JE, Pawlowski NE (1987) Enhancement of carcinogenesis by the natural anticar-cinogen indole-3-carbinol. J Natl Cancer Inst 78:931–934
Dashwood RH, Arbogast DN, Fong AT, Pereira CB, Hendricks JD, Bailey GS (1989) Quantitative inter-relationships between aflatoxin B1 carcinogen dose, indole-3-carbinol anticarcinogen dose, target organ DNA adduction and final tumor response. Carcinogenesis 10:175–181
Dashwood RH, Fong AT, Williams DE, Hendricks JD, Bailey GS (1991) Promotion of aflatoxin B1 carcinogesis by the natural tumor modulator indole-3-carbinol: influence of doses, duration, and intermittent exposure on indole-3-carbinol promotional potency. Cancer Res 51:2362–2365
Pence BC, Buddingh F, Yang SP (1986) Multiple dietary factors in the enhancement of dimethylhydrazine carcinogenesis: main effect of indole-3-carbinol. J Natl Cancer Inst 77:269–276
Ito N, Tsuda H, Tatematsu M, Inoue T, Tagawa Y, Aoki T, Uwagawa S, Kagawa M, Ogiso T, Masui T, Imaida K, Fukushima S, Asamoto M (1988) Enhancement effect of various hepato-carcinogens on induction of preneoplastic glutathione S-transferase placental form positive foci in rats—an approach for a new medium-term bioassay system. Carcinogenesis 9:387–394
Fukushima S, Hagiwara A, Hirose M, Yamaguchi S, Tiwawech D, Ito N (1991) Modifying effects of various chemicals on preneoplastic and neoplastic lesion development in a wide-spectrum organ carcinogenesis model using F344 rats. Jpn J Cancer Res 82:642–649
Hsu SM, Raine L, Fanger H (1981) Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and labelled antibody (PAP) procedures. J His-tochem Cytochem 29:577–580
Tatematsu M, Furihata C, Katsuyama T, Mera Y, Inoue T, Matsushima T, Ito N (1987) Immunohistochemical demonstration of pyloric gland-type cells with low pepsinogen isozyme 1 in preneoplastic and neoplastic tissues of rat stomachs treated with N-methyl-N′-nitro-N-nitrosoguanidine. J Natl Cancer Inst 78:771–777
Sparnins VL, Venegas PL, Wattenberg LW (1982) Glutathione S-transferase activity: enhancement by compounds inhibiting chemical carcinogenesis and by dietary constituents. J Natl Cancer Inst 68:493–496
Paolini M, Mesirca R, Gialluca N, Bauer C, Biagi GL, Cantelli-Forti G (1995) On cancer chemoprevention: complications and limitations of some proposed strategies. Carcinogenesis 16:971–973
Peraino CB, Michael RJ, Staffeldt EF (1971) Reduction and enhancement by phenobarbital of hepatocarcinogenesis induced in the rat by 2-acetaminofluorene. Cancer Res 32:1506–1512
Schuttle-Hermann R (1989) Tumor promotion in the liver. Arch Toxicol 57:147–158
Morse MA, Wang C-X, Amin SG, Hecht SS, Chung F-L (1988) Effects of dietary sinigrin or indole-3-carbinol on 0”-methyl-guanine-DNA-transmethylase activity and 4-(methylnitrosa-mino)-l-(3-pyridyl)-l-butanone-induced DNA methylation and tumorigenicity in F344 rats. Carcinogenesis 9:1891–1895
Hiasa Y, Kitahori Y, Konishi N, Ohshima M (1992) Chemical carcinogenesis in the thyroid gland. Toxicol Lett 64/65:389–395
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1997 Springer Japan
About this paper
Cite this paper
Kim, D.J., Ito, N., Tsuda, H. (1997). Enhancement by Indole-3-Carbinol of Liver and Thyroid Gland Neoplastic Development in a Rat Medium-Term Multiorgan Carcinogenesis Model. In: Ohigashi, H., Osawa, T., Terao, J., Watanabe, S., Yoshikawa, T. (eds) Food Factors for Cancer Prevention. Springer, Tokyo. https://doi.org/10.1007/978-4-431-67017-9_40
Download citation
DOI: https://doi.org/10.1007/978-4-431-67017-9_40
Publisher Name: Springer, Tokyo
Print ISBN: 978-4-431-67019-3
Online ISBN: 978-4-431-67017-9
eBook Packages: Springer Book Archive