| Summary: | Indole-3-carbinol (I3C) and butylated hydroxyanisole (BHA), anti-carcinogens
present in the human diet, were tested for their in vivo
and in vitro effect on aflatoxin B₁. (AFB₁) metabolism, and DNA adduct
formation in the rainbow trout. Dietary BHA at either 0.3 or 0.03%
had no effect on the hepatic tumor incidence of trout exposed to a 0.5
ppm AFB₁ solution as embryos, or when fed prior to and during dietary
exposure to 10 ppb AFB₁. Previous studies have shown 0.1% I3C to
inhibit AFB₁-induced hepatomas in trout. When fed at 0.2%, I3C
produced a 70% reduction in average in vivo hepatic DNA binding of
injected AFB₁ over a 21 day period compared to controls. A similar
study with 0.3% BHA had no effect on AFB₁-DNA binding over a 7 day
period. One hr incubations of AFB₁ with freshly isolated hepatocytes
from either BHA-, I3C- or control-fed trout showed no differences in
AFB₁ metabolism or DNA binding between BHA hepatocytes and controls.
However, I3C hepatocytes had 20% less DNA binding with a 2-fold
increase in aflatoxin M₁ production. Additions of 0, 1, 10 or 100 uM
BHA or I3C to hepatocytes isolated from trout fed a control diet had
no effect on AFB₁-DNA adduct formation except for a 20% decrease in
the 100 uM BHA hepatocytes. A 24 hr distribution study of injected [³H]-AFB₁ in trout fed 0.3% I3C showed less total radioactiuity in the
blood and liver at all times examined, compared to controls. These
reductions were accountable primarily as reduced levels of AFB₁ bound
to red blood cell DNA, reduced plasma levels of the metabolite
aflatoxicol (AFL), and decreased levels of AFB₁ and polar metabolites
in the liver of I3C trout. Total radioactivity was significantly
elevated in the bile of I3C fish resulting from a 7-fold increase in
aflatoxicol-n. glucuronide levels over controls. AFL glucuronide
levels were similar between treatments. Total radioactivity remaining
in the carcasses of I3C or control trout was similar.
These data indicate that I3C inhibits AFB₁ hepatocarcinogenesis
in trout through changes in carcinogen distribution, metabolism and
elimination leading to reduced initial DNA damage. BHA does not
appear to alter enzymes responsible for AFB₁ metabolism, and though it
may have a weak direct affect on AFB₁-DNA adduct formation, this does
not appear to be of importance in vivo since BHA had no effect on
AFB₁-induced carcinogenesis. === Graduation date: 1986
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