53-95-2Relevant articles and documents
Comparison of hprt and lacl mutant frequency with DNA adduct formation in N-Hydroxy-2-acetylaminofluorene-treated big blue rats
Chen, Tao,Mittelstaedt, Roberta A.,Aidoo, Anane,Patrice Hamilton,Beland, Frederick A.,Casciano, Daniel A.,Heflich, Robert H.
, p. 195 - 202 (2001)
N-Hydroxy-2-acetylaminofluorene (N-OH-AAF)is the proximate carcinogenic metabolite of the powerful rat liver carcinogen 2-acetylaminofluorene. In this study, transgenic Big Blue rats were used to examine the relationship between in vivo mutagenicity and DNA adduct formation by N-OH-AAF in the target liver compared with that in nontarget tissues. Male rats were given one, two, or four doses of 25 mg N-OH-AAF/kg body weight by i.p. injection at 4-day intervals, and groups of treated and control rats were euthanized up to 10 weeks after beginning the dosing. Mutant frequencies were measured in the spleen lymphocyte hprt gene, and lacl mutant frequencies were determined in the liver and spleen lymphocytes. At 6 weeks after beginning the dosing, the hprt mutant frequency in spleen lymphocytes from the four-dose group was 16.5 × 10-6 compared with 3.2 × 10-6 in control animals. Also at 6 weeks, rats given one, two, or four doses of N-OH-AAF had lacl mutant frequencies in the liver of 97.6, 155.6, and 406.8 × 10-6, respectively, compared with a control frequency of 25.7 × 10-6; rats given four doses had lacl mutant frequencies in spleen lymphocytes of 55.8 × 10-6 compared with a control frequency of 20.4 × 10-6. Additional rats were evaluated for DNA adduct formation in the liver, spleen lymphocytes, and bone marrow by 32P-postlabeling. Adduct analysis was conducted 1 day after one, two, and four treatments with N-OH-AAF, 5 days after one treatment, and 9 days after two treatments. N-(Deoxyguanosin-8-yl)-2-aminofluorene was the major DNA adduct identified in all the tissues examined. Adduct concentrations increased with total dose to maximum values in samples taken 1 day after two doses, and remained essentially the same after four doses. In samples taken after four doses, adduct levels were 103, 28, and 7 fmol/μg of DNA in liver, spleen lymphocytes, and bone marrow, respectively. The results indicate that the extent of both DNA adduct formation and mutant induction correlates with the organ specificity for N-OH-AAF carcinogenesis in the rat. Published 2001 Wiley-Liss, Inc.
A new short and efficient synthetic route to C8-N-acetylarylamine 2′-deoxyguanosine phosphoramidites
Boege, Nicolas,Krueger, Sarah,Schroeder, Marcus,Meier, Chris
, p. 3907 - 3914 (2008/09/18)
In addition to their C8-NH-arylamine-dG counterparts, C8-N-acetylarylamine adducts of 2′-deoxyguanosine (2′-dG) play an important role in the possible induction of chemical carcinogenesis. A new synthetic pathway of this adduct type using different aromatic amines has been developed following most probably an electrophilic amination reaction. These adducts can be converted into the corresponding phosphoramidites for incorporation into oligonucleotides. Georg Thieme Verlag Stuttgart.
Nucleophilic Substitution on the Ultimate Hepatacarcinogen N-(Sulfonatooxy)-2-(acetylamino)fluorene by Aromatic Amines
Novak, Michael,Rangappa, Kanchugarakoppal S.
, p. 1285 - 1290 (2007/10/02)
The kinetics and products of the reactions of the title compound 1 with aniline (5) and N,N-dimethylaniline (6) were investigated in MeOH.Addition of 5 (0.1-0.4 M) to a solution of 1 in MeOD-d4 has no effect on the overall rate of decomposition of 1 but generates a number of adducts (20-24) in moderate to high yield.The yields of all solvolysis products, except the rearranged O-sulfates 18 and 19, are suppressed by the addition of 5.The kinetic and product data are consistent with an SN1 mechanism (Scheme IV) in which 18 and 19 are generated by internal return from a tight ion pair, but all other products are generated by nucleophilic attack on a free nitrenium ion or solvent separated ion pair.The reaction of 6 with 1 shows similar characteristics to that of 5 with the exception that 6 reduces 1 in moderate yield to generate 2-(acetylamino)fluorene (25).This reduction occurs in competition with reaction to generate adducts (26, 27) similar to those obtained with 5.Kinetic and product data indicate that 25 is generated by reaction of 6 with a nitrenium ion intermediate.The differences in the behavior of 5 and 6 may be explained by cyclic voltammetry results which show that 6 is oxidized in MeOH more readily than 5 by about 2.5 kcal/mol.The reaction of 1 with 5 and 6 is considerably different from the rections of the same amines with the N-aryl-O-pivaloylhydroxylamines, which were previously shown to proceed via an SN2 mechanism.This change in mechanism may be attributed, in part, to increased steric hindrance at the nitrogen of 1 due to the N-acetyl group.
