Non-DIM, I3C Products are Immunotoxic

Non-DIM, I3C Products are Immunotoxic

Effects of indole-3-carbinol on immune responses, aberrant crypt foci, and colonic crypt cell proliferation in rats.

Exon JH, South EH, Magnuson BA, Hendrix K.

Department of Food Science and Toxicology, University of Idaho, Moscow 83844-2201, USA. jexon@uidaho.edu

J Toxicol Environ Health A. 2001 Apr 6;62(7):561-73.

Male Sprague-Dawley rats were treated orally with indole-3-carbinol (13C) for 7 wk at levels of 150, 100, and 50 mg/kg body weight. The rats were injected with 10 mg/kg body weight of the colon carcinogen, azoxymethane (AOM) on d 2 and 9 of 13C treatment. At termination of the study, all rats were assessed for immune function (humoral immunity, specific cell-mediated immunity, and nonspecific cell-mediated immunity). Colonic tissue was collected and examined for the presence of aberrant crypt foci (ACF) and proliferation of crypt cells. Antibody responses to antigen challenge were significantly suppressed in the animals exposed to the high dose of 13C. Delayed-type hypersensitivity responses, natural killer cell activity, the number and multiplicity of ACF, and cell proliferation parameters were not significantly different from those of the controls. Therefore, there was no clear protective or enhancing effect of 13C on ACF numbers or colonic cell proliferation indices. There was no strong correlation between changes in immune responses and the preneoplastic biomarkers of colon cancer.

Dietary indole-3-carbinol alters immune functions in rats.

Exon JH, South EH.

Department of Food Science and Toxicology, University of Idaho, Moscow 83844-2201, USA.

J Toxicol Environ Health A. 2000 Feb 25;59(4):271-9.

To further elucidate the physiological mechanisms that may contribute to the dichotomy of effect of indole-3-carbinol (I3C) on cancer development, we examined immune functions representative of the three major branches of the immune system in rats fed either a high (150 mg/kg) or low (50 mg/kg) dose of I3C. Animals fed the high dose of I3C daily for 7 wk had significantly reduced natural killer cell activity. In contrast, T-cell-mediated delayed-type hypersensitivity was significantly elevated. Antibody production in response to the antigen keyhole limpet hemocyanin was not significantly altered compared to controls. These results indicate that exposure to I3C may have differential effects on major immune responses. The significance of these immune function alterations in tumor development will require additional investigation of the effects of dietary I3C on immune functions in appropriate tumor models.

Effects of immunosuppressive chemicals on lymphoid development in foetal thymus organ cultures.

d'Argy R, Bergman J, Dencker L.

Department of Toxicology, Uppsala University, Sweden.

Pharmacol Toxicol. 1989 Jan;64(1):33-8.

A murine foetal thymus organ culture system was employed to screen a number of immunotoxic chemicals for direct thymus toxicity. The toxic effects caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its congeners on the system used had previously been shown to be similar to those caused in vivo on lymphoid development. The most potent compound tested was the corticosteroid fluocinolone acetonide, which caused a 50% inhibition of lymphoid development (EC50) at a concentration of 5 x 10(-11) M. The EC50 of TCDD was around 5 x 10(-10) M while that of 4 beta-phorbol 12-myristate 13-acetate (TPA) was ca 10(-7) M. TCDD and its congeners are believed to act via binding to the Ah receptor. Other known or presumed ligands of this receptor, which are potent inducers of P1-450 (P-448) -dependent polysubstrate monooxygenase activities, were considerably less toxic with EC50 levels varying between 10(-5) M (7,12-dimethylbenz(alpha-) antracene, alpha-naphthoflavone, benzo(alpha)pyrene) and 10(-4) M (beta-naphthoflavone and 3-methylcholantrene). Dinaphtho/2,3-b,5,6-b/dioxin and indolo/2,3-b/carbazole showed toxicity at 5 x 10(-6)-10(-5) M and 5 x 10(-5) M respectively. TCDD, TPA, and fluocinolone showed additive effects when added two by two in different combinations. Thus fluocinolone, known to counteract the toxicity and epidermal growth factor (EGF) cell-surface receptor-decreasing activity caused by TPA in other cell types, failed to decrease TPA toxicity in the thymus culture system.