Using salmonid microarrays to understand the dietary modulation of carcinogenesis in rainbow trout.

Abstract

The highlighted article in this issue by Tilton et al. (2005a) is an innovative approach to evaluate the modulation of estrogen receptor (ER) and aryl hydrocarbon (Ah)-receptor pathways as mechanisms underlying indole-3-carbinol (I3C) tumor promotion in rainbow trout (Onchorhynchus mykiss). I3C and its major in vivo component 3,3'-diindolylmethane (DIM) are potent tumor promoters that appear to target both of the aforementioned receptor pathways. However, the relative importance of I3C modulation of ER and AhR-dependent pathways in the promotion of rainbow trout hepatocarcinogenesis has not been established. Previously, researchers within this group reported that I3C promotes aflatoxin B1 (AFB1)-induced trout hepatocarcinogenesis post-initiation at low concentrations in the diet that induce the expression of vitellogenin, a downstream marker for the activation of ER-dependent pathways in fish. Furthermore, the promotional effects of I3C on AFB1 hepatocarcinogenesis in rainbow trout occur at concentrations that differentially induce vitellogenin, but not CYP1A expression. Interestingly, higher I3C concentrations induce the expression of both CYP1A and vitellogenin. Thus, the relative induction of vitellogenin and CYP1A expression, which are respective markers for activation of fish ER and AhR-mediated gene expression, suggest that these pathways may be important for tumor promotion by dietary I3C in trout. Understanding the complexities of I3C-mediated tumor promotion is essential from several perspectives. For example, there is the obvious need to increase our basic understanding of dietary modulation of carcinogenesis. In addition, I3C also exhibits significant antioxidant and cancer chemoprotective effects under certain experimental conditions and in certain models which have led to its recent marketing as a dietary supplement, as well as its development as a possible chemopreventive agent in humans.

• Authors: Evan P Gallagher
• Journal: Toxicological sciences : an official journal of the Society of Toxicology (Toxicol Sci) Vol. 90 Issue 1 Pg. 1-4 (Mar 2006) ISSN: 1096-6080 [Print] United States
• PMID: 16532552 (Publication Type: Comment, Journal Article)

Chemical References

• Carcinogens
• Indoles
• Receptors, Aryl Hydrocarbon
• Receptors, Estrogen
• Vitellogenins
• Aflatoxin B1
• indole-3-carbinol

Topics

• Aflatoxin B1 (toxicity)
• Animals
• Carcinogens (toxicity)
• Cocarcinogenesis
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic (drug effects)
• Indoles (toxicity)
• Liver Neoplasms, Experimental (chemically induced, genetics, metabolism)
• Oligonucleotide Array Sequence Analysis
• Oncorhynchus mykiss
• Receptors, Aryl Hydrocarbon (metabolism)
• Receptors, Estrogen (metabolism)
• Vitellogenins (metabolism)