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The Importance of 2-aminofluorene in the Mutagenic Activation of 2-acetylaminofluorene

The Importance of 2-aminofluorene in the Mutagenic Activation of 2-acetylaminofluorene

I G Robertson

Mutat Res. 1986 Nov;175(3):153-7.

PMID: 3534560

Abstract:

The mutagenic activation of 2-acetylaminofluorene (AAF) and its derivatives N-hydroxy-AAF and 2-aminofluorene (AF) by pulmonary and hepatic microsomal fractions from untreated rabbits was investigated using Salmonella strain TA98. The mutagenicity of AAF in the presence of hepatic microsomes followed typical saturation kinetics. However, in the presence of pulmonary microsomes, the mutagenic activity increased linearly with increasing substrate concentration and approximated that obtained with low concentrations of AF. N-Hydroxy-AAF was 1/10th as mutagenic as AF in the presence of pulmonary microsomes, but 2-2.5 times more mutagenic than AF in the presence of hepatic microsomes. The activation of AAF by both fractions was completely inhibited by the deacetylase inhibitor paraoxon. Although AAF does not appear to be a substrate for cytochrome P450 form 5, antibodies to this form inhibited the activation of AAF by pulmonary and hepatic microsomes by 90% and 60%, respectively. These results indicate that the mutagenic activation of AAF by these fractions primarily involves deacetylation to AF, followed by cytochrome P450 form 5-mediated activation of AF.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP153786	2-Aminofluorene		153-78-6	Price

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