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Tumor dose-response studies with aflatoxin B1 and the ambivalent modulator indole-3-carbinol: inhibitory versus
R H Dashwood1, A T Fong, J D Hendricks
1Department of Food Science and Technology, Oregon State University, Corvallis 97331.
Abstract:
Indole-3-carbinol (I3C), a natural compound from cruciferous vegetables, inhibits aflatoxin B1 (AFB1) carcinogenesis in trout when administered prior to and during carcinogen exposure, but also promotes it in the same species when given after AFB1 initiation. To provide quantitative potency information for these opposing activities, detailed tumor dose-response studies were performed with AFB1 (10-400 ppb) and I3C (0-4,000 ppm). In a plot of (logit) percent tumor response vs log AFB1 exposure, the results generated a series of parallel AFB1 dose-response curves. Increasing I3C doses displaced these curves, respectively, toward higher and lower AFB1 doses in the inhibition and promotion studies. Similar potencies were observed over the dose range 0-1,500 ppm I3C; the 50% promotion and inhibition (P50 and I50) values were 1,000 vs 1,400 ppm I3C, respectively. Differences in the protocols used in the two studies suggest that the inhibitory activity of I3C is more likely to supersede promotion under human exposure conditions.
Insights
Indole-3-carbinol (I3C) from cruciferous vegetables can inhibit or promote aflatoxin B1 (AFB1) carcinogenesis in trout. I3C’s inhibitory activity is more likely to prevail under human exposure conditions.
Area of Science:
- Toxicology
- Carcinogenesis Research
- Natural Product Chemistry
Background:
- Indole-3-carbinol (I3C) is a natural compound found in cruciferous vegetables.
- I3C exhibits dual effects on aflatoxin B1 (AFB1) carcinogenesis in trout, acting as both an inhibitor and promoter.
- Quantitative data on I3C's opposing activities are needed.
Purpose of the Study:
- To quantitatively assess the potency of Indole-3-carbinol (I3C) in inhibiting and promoting aflatoxin B1 (AFB1) carcinogenesis.
- To compare the dose-response relationships for I3C's inhibitory and promotional effects.
- To evaluate the likelihood of I3C's inhibitory activity under human exposure scenarios.
Main Methods:
- Detailed tumor dose-response studies were conducted using varying doses of AFB1 (10-400 ppb) and I3C (0-4,000 ppm) in trout.
- Logit-log plots of tumor response versus AFB1 exposure were analyzed to generate dose-response curves.
- The 50% promotion (P50) and inhibition (I50) values for I3C were determined.
Main Results:
- AFB1 exposure generated parallel dose-response curves for tumor incidence.
- Increasing I3C doses shifted these curves towards higher AFB1 doses (inhibition) or lower AFB1 doses (promotion).
- The potency for inhibition (I50 = 1,400 ppm I3C) and promotion (P50 = 1,000 ppm I3C) was similar within the 0-1,500 ppm I3C dose range.
Conclusions:
- Indole-3-carbinol (I3C) demonstrates both inhibitory and promotional effects on aflatoxin B1 (AFB1) carcinogenesis, with comparable potencies.
- Differences in study protocols suggest that I3C's inhibitory effects may be more dominant under conditions relevant to human exposure.
- Further research is warranted to fully elucidate the mechanisms and implications of I3C's dual role in carcinogenesis.