Detail of "6810-26-0"

Reference

Hepatic microsomal N-glucuronidation and nucleic acid binding of N-hydroxy arylamines in relation to urinary bladder carcinogenesis

Hepatic microsomal N-glucuronidation and nucleic acid binding of N-hydroxy arylamines in relation to urinary bladder carcinogenesis. Kadlubar, Fred F.; Miller, James A.; Miller, Elizabeth C. (Med. Cent., Univ. Wisconsin, Madison, Wis., USA). Cancer Res., 37(3), 805-14 (English) 1977. CODEN: CNREA8. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Uridine 5'-diphosphoglucuronic acid-fortified hepatic microsomes from dogs, rats, or humans rapidly metabolized 3H-labeled N-hydroxy-2-naphthylamine (I) [613-47-8] to a water-sol. product that yielded 98% of the parent N-hydroxyamine upon treatment with .beta.-glucuronidase.In this article, certain chemicals are used. Some of their cas registry numbers are 53-95-2 and 62317-15-1 The metabolite was identified as N-(.beta.-1-glucosiduronyl)-N-hydroxy-2-naphthylamine [62317-15-1] from UV, IR, and mass spectral analyses of the glucuronide and its nitrone deriv. Incubation of N-hydroxy-1-naphthylamine (N-HO-1-NA) [607-30-7], N-hydroxy-4-aminobiphenyl (N-HO-ABP) [6810-26-0], or the N-hydroxy derivs. of 2-aminofluorene [53-94-1], 4-aminoazobenzene [53-94-1], or N-acetyl-2-aminofluorene [53-95-2] with uridine 5'-diphosphoglucuronic acid-fortified hepatic microsomes also yielded water-sol. products. .beta.-Glucuronidase treatment released 80 to 90% of the N-OH-1-NA-3H and N-HO-ABP-3H conjugates as tritiated ether-extractable derivs. N-OH-1-NA, I, and N-HO-ABP and the glucuronides of these N-hydroxyarylamines were relatively stable and nonreactive near neutral pH. At pH 5, the N-glucuronide of I and the presumed N-glucuronides of N-HO-1-NA and N-HO-ABP were rapidly hydrolyzed to the N-hydroxyarylamines that were then converted to reactive derivs. capable of binding covalently to nucleic acids. These data support the concept that arylamine bladder carcinogens are N-oxidized and N-glucuronidated in the liver and that the N-glucuronides are transported to the urinary bladder. The hydrolysis of the glucuronides to N-hydroxyarylamines and the conversion of the latter derivs. to highly reactive electrophilic arylnitenium ions in the normally acidic urine of dogs and humans may be crit. reactions for tumor induction in the urinary bladder. .

Acetyl coenzyme A-dependent metabolic activation of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl and several carcinogenic N-hydroxy arylamines in relation to tissue and species differences, other acyl donors, and arylhydroxamic acid-dependent acyltransferases

Acetyl coenzyme A-dependent metabolic activation of N-hydroxy-3,2'-dimethyl-4-aminobiphenyl and several carcinogenic N-hydroxy arylamines in relation to tissue and species differences, other acyl donors, and arylhydroxamic acid-dependent acyltransferases. Flammang, Thomas J.; Kadlubar, Fred F. (Div. Biochem. Toxicol., Natl. Center Toxicol. Res., Jefferson, AR 72079, USA). Carcinogenesis (London), 7(6), 919-26 (English) 1986. CODEN: CRNGDP. ISSN: 0143-3334. DOCUMENT TYPE: Journal CA Section: 4 (Toxicology) Several carcinogenic N-hydroxyarylamines underwent an acetyl CoA (AcCoA) [72-89-9]-dependent binding reaction with DNA in the presence of liver cytosol. 58-05-9 and 1264-45-5 which are cas registry numbers are also used here. The binding of N-hydroxy-3,2'-dimethyl-4-aminoliphenyl (I) [70786-72-0] was comparable to that obsd. with N-hydroxy-4-aminobiphenyl [6810-26-0] and N-hydroxy-2-aminofluorene (II) [53-94-1] while that of N-hydroxy-N1-acetylbenzidine [71609-23-9] and N-hydroxy-2-naphthylamine [613-47-8] was quite less. The AcCoA-dependent activation was widely distributed in several rat issues and in hepatic cytosol from several species susceptible to arom. amine carcinogenesis. Using either I or II and rat hepatic cytosol, activation to DNA-bound products was also detected with acetoacetyl- [1420-36-6] and propionyl CoA [317-66-8], but not with folinic acid [58-05-9] or 6 other acyl CoAs. The AcCoA-dependent DNA binding of I with cytosol was 5-fold greater than that obtained with microsomal or mitochondrial/nuclear fractions. The cytosolic activity was insensitive to inhibition by esterase/deacetylase inhibitor while the activity of other subcellular fractions as completely inhibited. Using I, AcCoA-dependent DNA-binding activity was also detected in the hepatic cytosols from other animals. In contrast, N-hydroxy-N-acetyl [70786-73-1] deriv. was not activated to a DNA-binding metabolite. The AcCoA-dependent formation of N-acetoxyarylamines by cytosolic acetyltransferase(s) could serve as a major metabolite activating pathway in several species. .