Hello to everybody,
is the Prival modified Ames test already used to test the mutagenicity of azo compounds? Or there are some better or more reliable test available?
The Prival test basically differs from the standard Ames test for the metabolic activation and for the cofactor medium used: uninduced hamster liver S9 instead of Aroclor 1254-induced rat liver S9, FMN is added to the cofactor mix etc.
Are there some recent paper that compare S9 metabolic activation deriving from different species (eg. rat, hamster, human)? Apparently hamster shows a poor metabolic activity and hence greater toxicity than rat. For these reason, in a precautionary way, hamster S9 should be used instead of the more common rat S9 fraction (?).
I am not able to explain this phrase: "Rat liver S9 inhibited the ability of hamster S9 to activate benzidine to a mutagen" (taken from Prival M.J., 1982).
Thank you in advice,
Nicola
Hello Nicola,
The reason that Hamster S9 is more efficient at opening the azo bond is related to the relative reductive vs oxidative potential of the hamster S9 is greater then seen in rats or humans; in the latter oxidative enzymes predominate. I do not understand your third paragraph. I suggest that hamster S9 has a different metabolic profile to that of rat or human, this does not make it 'poorer' or more toxic, just different.
Prival did an experiment where they mixed hamster and rat S9, and in this case the mixture did not activate benzidine, hence rat S9 inhibited the hamster S9 ability to activate benzidine.
Not a complete answer to your questions but hopefully of some help.
Regards, Peter
Thank you for your clarification!
So maybe the rat S9 fraction contains a sort of inhibitor of the hamster S9, but this fraction is composed of various enzymes and what happened is not really clear...
Sincerely, Nicola
I don't know for sure the basis for the inhibition, but most likely the addition of the rat S9 pushed the balance towards oxidative metabolism and away from reductive metabolism, hence insufficient activation or opening of the azo bond for detection in the assay.
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