Indole-3-carbinol and related compound effects on biochemical parameters with respect to trout tumorigenesis Public Deposited


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  • Indole-3-carbinol (13C), a metabolite of glucobrassicin, is found in cruciferous vegetables. It is able to act as an inhibitor or promoter of carcinogenesis depending on the species, the carcinogen and when it is given in relation to the carcinogen. This is probably due to the fact that it reacts in an acid environment, such as the stomach, to form acid condensation products. Two of the many condensation products are lndolo(3,2-b)carbazole (ICZ) and 3,3'-diindolylmethane (133'). ICZ is a strong agonist for the Aryl hydrocarbon Receptor (AhR), but is present to a lesser extent in the reaction mix compared to other acid condensation products. 133' is the major condensation product of 13C, but is a weak AhR agonist. In this study, 13C, ICZ, 133' and Indolplex, a formulation of 133', were compared as to Vitellogenin (Vg) and CytochromelA P450 (CYP1A) induction as well as AFB1-initiated tumor promotion in rainbow trout. The initiated trout received 12 ppm AFB1 as fry, which is expected to result in a 10 to 15 percent increase in liver tumors. Vg is an egg yolk precursor is a biomarker for estrogenicity. The CYP1A gene belongs to a gene super-family that function in xenobiotic transformation, and its transcription is regulated by the AhR. Initially, trout were treated with 2000 ppm 13C, which was later lowered to 1000 ppm due to trout mortality. The treatment doses of ICZ and 133' coresponded to the percentage found in the normal reaction mix. ICZ treatments contained 0.3 ppm and 3 ppm. The 133' concentrations used were 400 ppm and 1200 ppm. IndolplexTM,used to treat Recurrent Respiratory Papillomatosis (RRP), contained 1200 ppm. Additionally, a comparison of Vg and CYP1A induction was done between this study and another that included compounds known to be tumor promoters. The other study included promoters believed to act through oxidative stress (hydrogen peroxide (H202), t-butyl peroxide and low choline diet), endocrine modulation (0-estradiol (E2), dehydroepiandrosterone (DHEA), perfluorooctanoic acid (PFOA) and through the AhR (R-naphthoflavone (BNF). These treatments were applied for 2 weeks. 13C, ICZ and 133' at the doses used induced Vg to about the same degree after 4 months of treatment in trout. 13C induced CYP 1A more than ICZ or 133'. Both ICZ and 133' seemed to have suppressor characteristics at the higher doses in relation to CYP1A induction. Vg and CYP1A induction did not correlate with tumor induction. Mortality was high throughout the experiment. After a year of treatment, tumor incidence was extremely high. In controls that were not treated with AFB,, there was an incidence of liver tumors of 8 percent. The normal incidence is 0.1 percent. Indolplex had the highest incidence of tumors, but was also the treatment with the highest survival of fish. More research needs to be done in relation to 13C and its acid condensation products. Also the cause of the high mortality and tumor rates needs to be found.
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