Developmental aspects of 2-acetamidofluorene metabolism and mutagenic activation in the chick

Abstract

1. Oxidative metabolism and mutagenic activation of 2-acetamidofluorene (AAF) in the Salmonella test system were studied with liver subfractions from untreated and β-naphthoflavone (BNF)-pretreated chicks during the first 10 days after hatching.

2. Newly hatched chicks had high liver microsomal mono-oxygenase activities, and these were markedly increased by BNF-pretreatment.

3. The mutagenic activation of AAF with control liver subfractions was highest on day 1 after hatching and declined towards day 10.

4. BNF-pretreatment caused decreases in the mutagenicity of AAF at high protein concentrations in the test system, but led to increases in mutagenic activity when low protein concentrations were applied.

5. N-Hydroxy-2-acetylaminofluorene was activated to a mutagen by microsomal metabolism, and this reaction was blocked by the deacetylase inhibitor paraoxon.

6. SDS polyacrylamide gel electrophoresis of liver microsomes from BNF-pretreated chicks showed an increase in a band with mol. wt. of approx. 55 000. The increase in the 55 000 mol. wt. band following BNF-pretreatment was associated with increases in benzo[a]pyrene hydroxylase and AAF N-hydroxylase activities in the chick liver microsomes.