Activation acetylaminofluorene

Kaderbhai MA et al. Alteration in the enzyme activity and polypeptide composition of rat endoplasmic reticulum during acute exposure to 2-acetylaminofluorene. Chem Biol Interact 1982 39 279-299. 

CYP1A2. CYP1A2 has been implicated in the activation of procarcinogenic species such as aflatoxin Bl, 2-acetylaminofluorene, and other arylamines. It tends to favor aromatic substrates, both heterocyclic aromatic substrates like caffeine and aromatic substrates like phenacetin (10). In the case of caffeine, 1A2 is the major isoform catalyzing the... 

C. C. Lai, E. C. Miller, A. Liem, The Essential Role of Microsomal Deacetylase Activity in the Metabolic Activation, DNA-(Deoxyguanosin-8-yl)-2-aminofluorene Adduct Formation and Initiation of Liver Tumors by A-Hydroxy-2-acetylaminofluorene in the Livers of Infant Male B6C3Fj Mice , Carcinogenesis 1988, 9, 1295-1302. 

N-Oxidation. (V-oxidation can occur in a number of ways, including hydroxylamine formation, oxime formation, and N-oxide formation, although the latter is primarily dependent on the FMO enzyme. Hydroxylamine formation occurs with a number of amines such as aniline and many of its substituted derivatives. In the case of 2-acetylaminofluorene the product is a potent carcinogen, and thus the reaction is an activation reaction (Figure 7.6). 

Banner et al., (21) found that selenium did not influence the acute alterations induced by 2-acetylaminofluorene or methylazoxymethanol and suggested that the anticarcinogenic properties of selenium were due to a mechanism other than an interference with carcinogen activation and interaction with cellular macromolecules. 

Acetylaminofluorene is biotransformed in the liver. 2-Acetylaminofluorene can stimulate cytochrome P450 lAl isozyme (CYPIAI) activity, inducing both CYPIAI and CYP1A2 proteins, whereas... 

Gao N, Aidoo A. Heflich RH. 1991. Analysis of rat lymphocyte activation of benzo[a]pyrene. 2-acetylaminofluorene, and several of their metabolites to mutagenic and DNA-damaging species in vitro. Teratogen Carcinog Mutagen 11(2) 65-76. 

The A-hydroxylation of acetylaminofluorene and paracetamol are two toxicologically important examples illustrating species differences (see Chapter 7). Another example is the metabolism of amphetamine, which reveals marked species differences in the preferred route, as shown in figure 5,8. Species differences in the rate of metabolism of hexobarbital in vitro correlate with the plasma half-life and duration of action in vivo as shown in table 5,10. This data shows that the marked differences in enzyme activity between species is the major determinant of the biological activity in this case. 

FIGURE 7.1 Some of the possible routes of metabolic activation of acetylaminofluorene (AAF). N-OH-AF N-hydroxyaminofluorene N-OH-AAF N-hydroxyacely/aminqfluorene N-acetoxy AF H-acetoxyaminofluorene N-(dG-8yl)-AF N-deoxyguanosinyl-aminofluorene N-(dG-8yl)-AAF N-deoxyguanosinyl-acetylaminofluorene. P-450 cytochrome(s) P-450 DA deacetylase NAT N-acetyltransferase AHAT N, O-arylhydroxamic acid acyltransferase. 

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