Dose-dependent inhibition of tobacco smoke carcinogen-induced lung tumorigenesis in A/J mice by indole-3-carbinol.

Cancer Prevention Research
Fekadu KassieStephen S Hecht

Abstract

Recently, we reported inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) plus benzo(a)pyrene (BaP)-induced lung tumorigenesis in A/J mice by indole-3-carbinol (I3C; 112 micromol/g diet) administered beginning at 50% in the carcinogen treatment phase. In this study, we examined the dose-dependent and postcarcinogen tumor-inhibitory activities of I3C. A mixture of NNK plus BaP (2 micromol each) administered by gavage as eight biweekly doses caused 21.1 +/- 5.2 lung tumors per mouse. Carcinogen-treated mice given diets containing I3C at 1, 10, 30, 71, and 112 micromol/g, beginning at 50% in the carcinogen treatment phase, had 17.9 +/- 6.1, 10.4 +/- 3.7, 9.8 +/- 5.1, 5.2 +/- 4.0, and 2.5 +/- 2.4 lung tumors per mouse, corresponding to reductions by 15%, 51%, 53%, 75%, and 88%, respectively. All reductions, except at the lowest dose level (1 micromol I3C/g diet), were significant (P < 0.001). Similarly, administration of I3C (112 micromol/g diet) beginning 1 week after the last dose of the carcinogen significantly reduced NNK plus BaP-induced lung tumor multiplicity to 5.6 +/- 3.5, corresponding to a reduction by 74%. Analyses of cell proliferation and apoptosis markers revealed that I3C reduced the number of Ki-67-p...Continue Reading

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Citations

Jun 25, 2009·Nature Reviews. Cancer·Stephen S HechtDorothy K Hatsukami
Dec 24, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Regan M Memmott, Phillip A Dennis
Nov 22, 2013·Reproductive Toxicology·Joyce Zalotti BrandtWellerson Rodrigo Scarano
Feb 20, 2010·Microscopy Research and Technique·Kameswaran RavichandranRamanibai Ravichandran
Jun 5, 2015·Acta Biochimica Et Biophysica Sinica·Guang-Zhe GeCeshi Chen
Feb 4, 2016·Molecular Nutrition & Food Research·Naomi FujiokaStephen S Hecht
Mar 26, 2010·International Journal of Toxicology·Wei ZhuXingfen Yang
Dec 18, 2019·International Journal of Radiation Biology·Vinita ChauhanRobert Stainforth

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