N-hydroxy-2-aminofluorene

SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

EVIDENCE OF 2-FLUORENYLHYDROXYLAMINE PRODUCING EAR DUCT, BREAST & LOCAL TUMORS FROM SC INJECTION INTO RATS. /FROM TABLE/

CALF THYMUS DNA WAS MODIFIED IN VITRO WITH G-(3)H-LABELED N-HYDROXY-2-AMINOFLUORENE & N-ACETOXY-N-ACETYL-2-AMINOFLUORENE & THE NUCLEASE S1 DIGESTION WAS STUDIED UNDER IDENTICAL CONDITIONS. THE RATIOS OF THE MAXIMUM REACTION RATE & THE MICHAELIS CONSTANT, V/KM, INDICATED THAT 2-AMINOFLUORENE MODIFIED DNA WAS HYDROLYZED 3 TIMES MORE SLOWLY THAN N-ACETYL-2-AMINOFLUORENE MODIFIED DNA UNDER SIMILAR REACTION CONDITIONS. THE 2-AMINOFLUORENE MODIFIED DNA WAS SLIGHTLY MORE SUSCEPTIBLE TO PARTIAL DIGESTION BY NUCLEASE S1 THAN UNMODIFIED CONTROL DNA. APPARENTLY, THE LOCAL REGIONS OF DENATURATION INDUCED BY 2-AMINOFLUORENE SUBSTITUTION WERE SMALLER THAN THOSE ASSOCIATED WITH N-ACETYL-2-AMINEFLUORENE MODIFICATION.

THE MAJOR AMINOFLUORENE-DNA DERIVATIVE FORMED FROM THE CARCINOGEN N-ACETYL-2-AMINOFLUORENE IN VIVO IN RAT LIVER IS N-(DEOXYGUANOSIN-8-YL)-2-AMINOFLUORENE. SIMILAR PRODUCTS WERE ISOLATED FROM ENZYMIC HYDROLYZATES OF DNA REACTED WITH N-HYDROXY-2-AMINOFLUORENE.

N-hydroxy-2-aminofluorene was evaluated in the mammalian cell CHO/HGPRT gene mutation assay at a dose range of 80-525 umol. The test protocol used met criteria established for this assay by the Gene-Tox Program. The chemical was positive at the 80 umol dose level without metabolic activation.

Activation of 2-AAF /2-acetylaminofluorene/ to N-hydroxy-2-aminofluorene, a potent mutagen to Salmonella strains, by guinea-pig liver (S-9) mix afforded 2-aminofluorene as well as N-OH-AAF /N-hydroxy-acetylaminofluorene/. Mutagenicities of 2-aminofluorene & N-hydroxy-acetylaminofluorene were inhibited by antisera against NADPH-cytochrome C reductase & by paroxon. While the mutagenic activity of 2-acetylaminofluorene to N-hydroxy-2-aminofluorene can be produced by N-hydroxylation of 2-aminofluorene or deacetylation of N-hydroxy-2-aminofluorene, the data suggested that deacetylation of 2-acetylaminofluorene (to 2-aminofluorene), followed by N-hydroxylation to produce N-hydroxy-2-aminofluorene, was the main pathway for the mutagenic activation of 2-acetylaminofluorene by guinea pig liver (S-9) mix.

EVIDENCE FOR THE DIRECT ACETYLATION OF N-HYDROXY-2-AMINOFLUORENE CATALYZED BY RAT LIVER CYTOSOL HAS BEEN OBTAINED.

THE O-GLUCURONIDE OF N-HYDROXY-2-FLUORENAMINE IS A MUCH MORE REACTIVE ELECTROPHILE THAN ITS ACETYLATED DERIVATIVE &, IF FORMED IN VIVO, COULD BE AN IMPORTANT REACTIVE FORM /IN NEOPLASM INDUCTION/.

N-HYDROXY-2-FLUORENAMINE, AN ELECTROPHILIC REAGENT AT ACIDIC PH'S, HAS LITTLE, IF ANY, REACTIVITY AT NEUTRALITY. EARLIER REPORTS ON THE APPARENT REACTIVITY OF THIS HYDROXYLAMINE ON INCUBATION WITH LIVER PREPARATIONS ... APPEAR TO BE A CONSEQUENCE OF N-ACETOXY-2-FLUORENAMINE FORMATION. THIS VERY REACTIVE ESTER IS FORMED BY THE ENZYMATIC TRANSFER OF THE N-ACETYL GROUP OF N-HYDROXY-2-FLUROENYLACETAMIDE TO THE OXYGEN OF THE HYDROXYLAMINE. THIS REACTION IS OF ... INTEREST SINCE STRONGLY REACTIVE ACETIC ACID ESTERS OF SEVERAL OTHER CARCINOGENIC AROMATIC HYDROXYLAMINES ARE FORMED BY THE SAME, OR SIMILAR, ENZYME SYSTEMS & SINCE A NUMBER OF TISSUES CATALYZE THE REACTION.

KINETIC STUDIES OF THE HYDROLYSIS REACTION SHOWED THAT IT OCCURS ALREADY AT A MEASURABLE RATE AT PH 9.5 & 37 °C. THE REACTION IS CATALYZED BY MAGNESIUM AND MANGANESE IONS & BY ALKALINE PHOSPHATASE FROM ESCHERICHIA COLI.

N-hydroxy-2-aminofluorene has known human metabolites that include N-hydroxy-2-aminofluorene, O-acetyl.

Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.

Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.