Fluorene Metabolism

Stringfellow, W. T. and Aitken, M. D. (1995). Competitive metabolism of naphthalene, methylnaphthalenes and fluorene by phenanthrene-degrading pseudomonads, Appl. Environ. Microbiol., 61, 357-362. 

Figure 7.1 Some of the possible routes of metabolic activation of AAF. Abbreviations-. AAF, acetylamino-fluorene N-OH-AF, /V-hydroxyaminofluorene N-OH-AAF, /V-hydroxyacetylaminofIuorene A/-acetoxy AF, N-acetoxyaminofluorene N-(dG-8yl)-AF, AAdeoxyguanosinyl-aminof I uo rene N-(dG-8yl)-AAF, A/-deoxyguanosinyl-acety-laminofluorene P-450, cytochrome(s) P-450 DA, deacetylase NAT, A/-acetyltransferase AHAT, N, O-arylhydroxamic acid acyltransferase.

Se inhibits 2-acetylamino-fluorene-induced hepatic damage and tumorogeneis in part by shifting metabolism towards detoxification... 

PAHs have generally not been detected in surveys of human tissue, presumably because the compounds are fairly rapidly metabolized. Phenanthrene was the only PAH detected in the 1982 National Human Adipose Tissue Survey it was found in trace concentrations in 13% of the samples (EPA 1986). Acenaphthylene, acenaphthene, fluorene, and chrysene were not found at levels below the detection limit (0.010 pg/g 10 ppt). However, autopsies performed on cancer-free corpses found PAH levels of 11-2,700 ppt (ng/g) in fat samples (Obana et al. 1981). Several PAHs were detected, including anthracene, pyrene, benzo[e]pyrene, benzo[k]fluoranthene, benzo[a]pyrene, and benzo[g,h,i]perylene, with pyrene being detected in the highest concentrations. A similar study done on livers from autopsied cancer-free corpses found levels of 6-500 ppt (ng/g) of all of the same PAHs except benzo[e]pyrene, which was not detected (Obana et al. 1981). As in the fat sample studies, pyrene appeared in the highest concentrations in the liver, but the overall levels were less than in fat. 

Moore BP, Hicks RM. Knowles MA. et al. 1982. Metabolism and binding of benzo[a]pyrene and 2 acetylamino fluorene by short-term organ cultures of human and rat bladder. Cancer Res 42 642-648. 

The genus Staphylococcus is traditionally associated with disease in humans, but the demonstration (Monna et al. 1993) that a strain of S. auriculans — isolated by enrichment with dibenzofuran and with no obvious clinical association — could degrade this substrate and carry out limited biotransformation of fluorene and dibenzo-1,4-dioxin may serve to illustrate the unsuspected metabolic potential of facultatively anaerobic Gram-positive organisms. 

FIGURE 27.13 Extracted ion chromatograms for C2-naphthalenes (ion 156, at 14 days, a), C3-naphthalenes (ion 170, at 28 days, b), Ci-fluorenes (ion 180, at 14 and 28 days, c), Ci-phenanthrenes (ion 192, at 14 and 28 days, d), and Ci-dibenzothiophenes (ion 198, at 14 and 28 days, e) in the source sterile control PB oil and the corresponding positive controls under standard fresh water biodegradation conditions. The circled peaks indicate the characteristic changes in distribution within isomers that were preferentially altered by biodegradation and/or co-metabolic oxidation. 

PROBABLE FATE photolysis, may be important, but is probably impeded by adsorption, photooxidation by U.V, in aqueous medium (Ty 90-95°C time for the formation of CO, (% of theoretical) 25% 75.3 hr, 50% 160.6 hr, 75% 297.4 hr, photooxidation half-life in air 6.81 hrs-2.i du>s, degrades quickly by photochemically produced hydroxyl radicals, with an estimated half-life of 29 hr oxidation-, chlorine and/or ozone in sufficient quantities may oxidize fluorene hydrolysis, not an important process volatilization probably not an important transport process, volatilization half-lives from a model river and a model pond 15 and 167 respectively sorption adsorption onto particles, biota, and sediments is probably the dominant transport process, half-life in soil ranges from 2-64 days biological processes bioaccumulation is short-term, metabolization and biodegradation are very important fates in estuarine waters 15pg/L, 12% adsorbed on particles after 3 hr... 

Fig. 6. Relationship between rate of in vivo metabolism and tissue xenobiotic concentration for the pooled data of a variety of aliphatic and aromatic hydrocarbons (naphthalene, anthracene, phen-anthrene, fluorene, BaP and hexadecane) and crustacean species. The equation of the log-log regression is given by logj (rate ofmetabolism in pmol min" g" ) = -0.898+ 0.930[log,o(tissue cone, in nmol g )] correlation coefficient = 0.983 (n = 17) 95% confidence limits for the regression line shown on the graph. Also shown on the graph, but not included in the regression, is the datum point from Table 21 for the metabolism of BaP by Homarus americanus ( ...

S. S. Thorgeirsson, S. Sasaki, and R. H. Adamson, Induction of monooxygenase in rhesus monkeys by 3-methylcholanthrene Metabolism and mutagenic activation of A -acetylamino-fluorene and benzo(a)pyrene,/. Natl. Cancer Inst. 60, 365-369 (1977). 

Crustaceans also exhibit a range in ability to biotransform PAHs. A study with the blue crab (Callinectes sapidus) found that this species was able to extensively metabolize PAHs (naphthalenes, fluorene, and benzo-[a]pyrene) and produce high concentrations of metabolites (Lee et al. 1976). Conversely, Burns (1976) found that another crab (Uca pugnax) possessed a very weak, uninducible microsomal MFO system for metabolizing xenobi-otic hydrocarbons. It was noted that this species was very sensitive to oil pollution because of its limited ability to metabolize hydrocarbons. The larval spot shrimp (Pandalus platyceros) only weakly metabolized naphthalene with 9%-21% of the total " C-naphthalene in tissues present as metabolites (Sanborn and Malins 1977). Contrary to this, fairly extensive biotransformation of naphthalene was demonstrated for the copepod Calanus helgolandicus by Corner et al. (1976) and Harris et al. (1977). 

In fish, the half-lives of PAHs are generally very short. Half-lives of 6-9 days for fluorene, phenanthrene, anthracene, and fluoranthene were reported in rainbow trout [Oncorhynchus mykiss (Salmo gairdneri)] fed oil spiked with PAHs (Niimi and Palazzo 1986). Niimi and Dookhran (1989) also reported half-lives of 1-4 d for acenaphthylene, methylanthracene, triphenylene, and perylene in rainbow trout. They reported a much longer half-life (25 d) for phenylnaphthalene compared to other PAHs and speculated that it may be more recalcitrant to metabolism because its aromatic rings are not all fused. 

Metabolism of fluorene in the rabbit results in both 2-hydroxyfluorene (XXXVII) and a compound which analyzes correctly for a hydrate of its glucuronoside, m.p. 214-215° (294). 

The direct cytotoxic effect of sixteen PAHs was evaluated by Schirmer et al. (1998a) in a cell line of gills of the rainbow trout (RT Gill-Wl) by assays with fluorescent dyes. Only the PAHs composed by 2 or 3 benzene rings (naphthalene, acenaphthylene, acenaphthene, fluorene and phenanthrene) presented cytotoxic effects on the cells without metabolic activation. In this way, the authors suggest that factors such as solubility in water and the lipophilic property are characteristics directly related with the cytotoxicity of the PAHs, which make them capable of altering the integrity of the cellular membrane when they are accumulated in it. 

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