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Activation of the mutagens of beef extract in vitro and in vivo

The activation in vitro of the mutagens isolated from beef extract, when tested with Salmonella typhimurium strain TA1538, requires the presence of S9 fractions from livers of PCB- or 3-methylcholanthrene-induced rats. S9 fractions from uninduced rats were unable to activate the mutagens, but no induction was necessary with Swiss albino mice. CD-1 mice had intermediate activation capabilities, which increased after the addition of 0.75% BHA to their diet. Human S9 were poor activators. No activation was observed with whole homogenates. The active metabolites formed were unstable at 37°C and firmly bound to protein.When isolated livers were perfused for activation, no inherently active mutagens were released into the perfusate. Similarly, no active mutagens were found in the urine of mice after administration to them of beef extract mutagens p.o. or i.p. Intrasanguine host-mediated assay did not show any significant mutagenic effect. The possibility that genotoxic effects of these compounds might be confined to metabolically competent cells of induced animals is discussed.

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