Inhibition of aflatoxin B¹ carcinogenesis in rainbow trout by flavone and indole compounds

Abstract

Several compounds such as flavonoids, selenium, antioxidants and retinoids reportedly reduce the induction of cancer in experimental animals, and some have been suggested to function by affecting the mixed-function oxidase (MFO) system. The following compounds: 50 and 500 p.p.m. beta-naphthoflavone (BNF), 1000 p.p.m. flavone, 1000 p.p.m. of a tangeretin - nobilitin mixture, 1000 p.p.m. beta- ionone , 1000 p.p.m. indole-3-carbinol ( I3C ) and 2000 p.p.m. quercetin were examined for protection against aflatoxin B1 (AFB1) hepatocarcinogenesis, induction of the MFO system and metabolism of AFB1 in rainbow trout. These compounds were fed to fingerling rainbow trout for 8 weeks. At that time the activity of several MFO enzymes and cytochrome P450 content were measured and the trout were exposed for 2 weeks to 20 p.p.b. AFB1 in the same diets. After feeding the test diets without AFB1 for another 6 weeks and basal diet for another 52 weeks, the tumor incidence was determined. The effect of BNF and I3C on in vivo binding of AFB1 to DNA was also measured in separate groups of trout. BNF induced the trout MFO system in a dose-dependent manner, tangeretin - nobilitin was less effective and I3C did not induce. BNF showed significant alterations in the metabolism of AFB1 to aflatoxicol and aflatoxin M1 using cell fractions from pretreated fish. None of the other compounds, including I3C showed such an effect. Despite the apparent lack of in vitro effect of I3C , both BNF and I3C reduced AFB1 - DNA binding in vivo. I3C and BNF provided marked protection against AFB1-induced hepatocarcinogenesis, while the other compounds were less effective. The 58 weeks tumor incidences were 4% for 1000 p.p.m. I3C , 6% for 500 p.p.m. BNF and 18% for 50 p.p.m. BNF, compared to 38% for the AFB1-positive control. These data demonstrate that gross induction of the MFO system was not necessarily required for alterations in DNA adduct formation in vivo or protection against AFB1 carcinogenesis. Both BNF and I3C provided marked protection but only BNF induced the MFO system.

Single-Dose and Multiple-Dose Administration of Indole-3-Carbinol to Women: Pharmacokinetics Based on 3,3′-Diindolylmethane

“…I3C has been shown to have pronounced chemopreventive effects against development of both spontaneous (4,6) and chemically induced (1-3, 5, 7-10) tumors in rats, mice, and trout. These chemopreventive effects of I3C were reported against tumor development in mammary gland (1,4,7), liver (2,3), lung (5,8), cervix (6,9), and gastrointestinal tract (1). This observation of a chemopreventive effect of I3C in a range of species and organ sites supports the further study and development of this compound.…”

“…Although most animal studies with I3C and carcinogen treatment have shown chemopreventive effects (1)(2)(3)(4)(5)(6)(7)(8)(9)(10), some experimental models have instead pointed to a tumorpromoting effect of this compound (11)(12)(13)(14). In contrast to the reported chemopreventive effects of I3C, the apparent promoting effects of I3C are highly dependent on the species, carcinogen, target organ, and exposure regimens employed (12,13).…”

Effects of 5,6-benzoflavone, indole-3-carbinol (I3C) and diindolylmethane (DIM) on chemically-induced mammary carcinogenesis: Is DIM a substitute for I3C?

“…The compound binds to the Ah receptor (AhR) and induces transcriptional activation of a wide variety of phase I/ II drug metabolizing enzymes (1,2). 5,6-BF was examined as a potential chemopreventive agent as early as the mid 1970's, and proved to be capable of inhibiting 7,12-dimethylbenzanthracene (DMBA)-induced mammary, lung, and aflotoxin B1-induced hepatocarcinogenesis (3)(4)(5).…”

A Phase I Study of Indole-3-Carbinol in Women: Tolerability and Effects

“…Cruciferous vegetables and specific compounds they contain have been shown to modulate carcinogenesis in animals and humans (1)(2)(3)(4)(5)(6)(7)(8)(9)(10). Among these compounds is glucobrassicin (3-indolylmethyl glucosinolate).…”