|Abstract or Summary
- Aflatoxin B₁ (AFB₁,) is a potent liver carcinogen to a number
of animal species including rainbow trout (Salmo gairdneri).
Microsomal activation is required for the in vitro conversion of
AFB, to a reactive metabolite, thought to be the AFB₁,-2,3-oxide,
which will bind nucleic acids, produce toxicity, and cause mutagenesis.
Nucleic acid-AFB₁ adduct formation is believed to be
an indication of cancer initiation.
Initial time-course and dosage experiments were conducted to
establish fundamental binding data in rainbow trout. Dietary casein
and fish protein concentrate (FPC) fed at 40, 50, 60, or 70% in
the diet, and cyclopropenoid fatty acids (CPFA), were measured for
their effect on in vivo AFB₁, binding to trout liver DNA. Both were
previously reported to dramatically alter AFB₁, induced hepatocarcinogenesis.
Rainbow trout and coho salmon (Oncorhynchus kisutch),
two Salmonid species varying greatly in their sensitivity to AFB₁,
were compared for their relative ability to produce AFB₁-DNA adducts.
Correlations between trout liver mixed function oxidase
(MFO) activity and AFB₁, binding to trout liver DNA were attempted
by use of β-napthoflavone, a powerful enzyme inducer in rainbow
Binding of AFB₁, to trout liver DNA over the 48 hour(h) period
studied reached a maximum value at 24 h. Increasing AFB₁, dosage
produced a linear response in AFB₁-DNA adduct formation. Binding
was significantly greater in the 70% casein fed fish than in the
70% FPC group. Binding in the 40, 50, and 60% casein fish was
non-significantly greater than the corresponding FPC groups.
AFB₁, binding to liver DNA was greatest in each source at the 60%
protein level. Binding in rainbow trout was at least 20-fold greater
by comparison than in coho salmon. CPFA reduced AFB₁, binding
to trout liver DNA at each protein diet employed, although non-significantly.
Pretreatment of fish with β-napthoflavone reduced
the total level of AFB₁ in the liver and AFB₁-DNA adduct formation
by 55 and 40%, respectively. Dietary protein and CPFA apparently
alter tumor formation through promoter effects since binding was
unaffected. The tumor resistance of coho salmon and β-napthoflavone
pretreated animals is possibly due to reduced initiation of
of the toxic lesion.