Aflatoxin B₁ (AFB₁) is a mold-produced toxin which has been shown
to be a potent hepatocarcinogen in many animal species. Of the
species studied thus far, rainbow trout have proven to be the most
sensitive. Experiments were conducted to investigate various aspects
of AFB₁ metabolism in this species, including in vitro mutagenesis,
and effects of dietary modifiers of AFB, carcinogenesis on in vitro
metabolism and mutagenesis. A comparative study of AFB₁ metabolism in
two salmonid species was also conducted.
In the first study, the relative mutagenic potencies of several
alfatoxin metabolites were evaluated using a trout liver fraction
system. Preliminary studies characterizing trout liver fractions for
use as an activation system were described. The results from
comparative mutagenicity experiments demonstrated that in vitro
mutagenic potencies qualitatively correlated with the in vivo
carcinogenic activities of various aflatoxins in rainbow trout. The
importance of these findings is discussed.
In the second study fish hepatocytes were characterized to
examine possible differences in activation of AFB₁ to bacterial
mutagens by hepatocytes from rainbow trout and coho salmon, two
species which are known to differ markedly in sensitivity to the
carcinogenic effects of AFB₁. Activation efficiency was approximately
three times greater in hepatocytes from trout compared to salmon. A
more marked difference was seen when S20 liver fractions from the two
species were used. Analysis of unbound [³H]AFB₁ metabolites revealed
that trout hepatocytes metabolized [³H]AFB₁ to a greater extent than
salmon. The results accurately reflected in vivo carcinogenesis
trends in salmonid fish.
Additional experiments were conducted to evaluate the effects of
dietary modifiers of AFB₁ carcinogenesis on in vitro mutagenesis and
metabolism of AFB₁.
Dietary β-naphthoflavone (β-NF) was shown to induce the
production of a novel trout metabolite of AFB₁, aflatoxicol M₁
(AFL-M₁). AFL-M₁ exhibited a mutagenic potency less than AFB₁ or
aflatoxicol (AFL), but greater than that of aflatoxin-M₁ (AFM₁).
Dietary β-NF, however, appeared to have no effect on in vitro
mutagenic activation of AFB₁ using hepatocytes or liver S20 fraction
from trout.
Dietary PCBs (Aroclor 1254) was shown to significantly decrease
in vitro mutagenesis of AFB₁, which reflected a similar PCB-mediated
inhibitory effect on AFB₁ carcinogenesis in trout in vivo.
Cyclopropenoid fatty acids (CPFAs) present in the diet (0-600
ppm) were shown to have no effect on in vitro mutagenesis of AFB₁,
indicating CPFAs may not significantly alter in vivo initiation of
AFB₁ carcinogenesis. / Graduation date: 1983
| Identifer | oai:union.ndltd.org:ORGSU/oai:ir.library.oregonstate.edu:1957/27463 |
| Date | 17 September 1982 |
| Creators | Coulombe, Roger A. |
| Contributors | Nixon, Joseph E. |
| Source Sets | Oregon State University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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