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

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.