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

Abstract

Several compounds such as flavonoids, selenium, anti-oxidants 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. β-naphthoflavone (BNF), 1000 p.p.m. flavone, 1000 p.p.m. of a tangeretin-nobilitin mixture, 1000 p.p.m. β-ionone, 1000 p.p.m. indole-3-carbinol (13C) and 2000 p.p.m. quercetin were examined for protection against aflatoxin B, (AFB 1 ) hepatocardnogenesis, induction of the MFO system and metabolism of AFB 1 in rainbow trout. These compounds were fed to fingerting 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. AFB 1 in the same diets. After feeding the test diets without AFB 1 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 AFB 1 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 AFB 1 to aflatoxicol and aflatoxin M 1 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 AFB 1 - DNA binding in vivo . I3C and BNF provided marked protection against AFB induced hepatocardnogenesis, while the other compounds were less effective. The 58 weeks tumor incidences were 4% for 1000 p.p.m. DC, 6% for 500 p.p.m. BNF and 18% for 50 p.p.m. BNF, compared to 38% for the AFB 1 -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 AFB 1 carcinogenesis. Both BNF and I3C provided marked protection but only BNF induced the MFO system.