Tumor Dose-Response Studies with Aflatoxin B1 and the Ambivalent Modulator Indole-3-Carbinol: Inhibitory Versus Promotional Potency

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 130 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.