Some historical aspects of N-aryl carcinogens and their metabolic activation.

Miller, James A.; Miller, Elizabeth C.

doi:10.1289/ehp.83493

Cited by 86 publications

(18 citation statements)

References 59 publications

(30 reference statements)

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Section: Benzidinementioning

confidence: 99%

“…This observation, plus DAB's high molar extinction coefficient at visible wavelengths (which facilitated its study in the days preceding radiolabeled compounds), resulted in a number of investigations being conducted with this aminoazo dye (2). The first step in the metabolic activation of DAB is a cytochrome P-450-catalyzed oxidative N-demethylation to N-methyl-4-aminoazobenzene (MAB) (2,77). Since a second N-demethylation, which yields 4-aminoazobenzene (AB), generally results in a decrease in carcinogenicity, most studies have concentrated on MAB, which is further activated by FMOcatalyzed N-oxidation to N-hydroxy-MAB and then is converted to an ultimate carcinogen through PAPS-dependent formation of N-sulfonyloxy-MAB.…”

Section: Benzidinementioning

confidence: 99%

“…Aromatic amines and amides were originally associated with the induction of bladder tumors in man and have subsequently been found to be carcinogenic at a number of sites in a variety of experimental animals (1,2). The initial step in the metabolic activation of these compounds usually involves an N-oxidation ( Fig.…”

Section: Introductionmentioning

confidence: 99%

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Formation and persistence of arylamine DNA adducts in vivo.

Beland¹,

Kadlubar²

1985

Environ Health Perspect

194

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Aromatic amines are urinary bladder carcinogens in man and induce tumors at a number of sites in experimental animals including the liver, mammary gland, intestine, and bladder. In this review, the particular pathways involved in the metabolic activation of aromatic amines are considered as well as the specific DNA adducts formed in target and nontarget tissue. Particular emphasis is placed on the following compounds: 1-naphthylamine, 2-naphthylamine, 4-aminobiphenyl, 4-acetylaminobiphenyl, 4-acetylamino-4'-fluorobiphenyl, 3,2'-dimethyl-4-aminobiphenyl, 2-acetylaminofluorene, benzidine, N-methyl-4-aminoazobenzene, 4-aminoazobenzene, and 2-acetylaminophenanthrene.

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Section: Benzidinementioning

confidence: 99%

Section: Benzidinementioning

confidence: 99%

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Formation and persistence of arylamine DNA adducts in vivo.

Beland¹,

Kadlubar²

1985

Environ Health Perspect

194

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“…1) In contrast, these N-arylacylamides are deacylated to the corresponding arylamines, and this process also contributes the toxicity of N-arylacylamides. [2][3][4][5] 2-Acetylaminofluorene and 2-formylaminofluorene, typical carcinogenic aromatic acylamines, were reported to be deacylated in animal bodies.…”

Section: Introductionmentioning

confidence: 99%

Deacylation of N-Formylanilines and N-Acetylanilines by Rat Liver Formamidase

Kawa

Ueda

Sugihara

et al. 2003

JOURNAL OF HEALTH SCIENCE

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The deacylation of N-formylanilines and Nacetylanilines to aniline derivatives was examined in rat liver preparations. When N 4 -formylsulfanilamide or N 4 -acetylsulfanilamide was incubated with rat liver cytosol, the deacylated metabolite, sulfanilamide, was formed. These deacylating activities were inhibited by paraoxone and diisopropyl fluorophosphate, inhibitors of formamidase. N 4 -Formylsulfanilamide and N 4 -acetylsulfanilamide were deacylated by formamidase purified from rat liver cytosol. N-Acetyl-or Nformylanilines bearing an electron-withdrawing group at the para position were deacylated to anilines by formamidase. In contrast, anilines bearing an electron-donating group at the para position were formylated to N-formylanilines in the presence of Nformyl-L-kynurenine. Formamidase catalyzed both Nformylation of aniline derivatives, and deacylation of N-formylanilines and N-acetylanilines.

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“…These arylamines are also acylated to N-arylacetamide and N-arylformamide, which are themselves toxic. Several reports have indicated that arylacetamides and arylformamides are further activated by hydroxylation to the corresponding hydroxamic acids, and N-hydroxy-2-acetylaminofluorene is further activated by sulfate conjugation in mammalian species (Miller and Miller, 1983). In contrast, these N-arylacylamides are deacylated to the corresponding arylamines, and this process also contributes to the toxicity of N-arylacylamides (Glinsukon et al, 1980;Aune et al, 1985;Land et al, 1989).…”

mentioning

confidence: 99%

Deacylation of N-Arylformamides andN-Arylacetamides by Formamidase in Rat Liver

Ueda

Kawa²,

Ohta³

2002

Drug Metab Dispos

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ABSTRACT:The in vitro deacylation of N-arylformamides and N-arylacetamides to arylamines was examined in rat liver preparations. When 2-acetylaminofluorene or 2-formylaminofluorene was incubated with rat liver microsomes or cytosol, the deacylated metabolite, 2-aminofluorene, was formed. The deacylating activity of liver microsomes was inhibited by bis(4-nitrophenyl)phosphate and phenylmethanesulfonyl fluoride, inhibitors of carboxylesterase. In contrast, the activity of liver cytosol was inhibited by diisopropyl fluorophosphate, an inhibitor of formamidase.Deacylation of these compounds appear to be mainly catalyzed by carboxylesterase in liver microsomes and formamidase in liver cytosol. 2-Formylaminofluorene, 2-acetylaminofluorene, 1-formylaminopyrene, 4-formylaminobiphenyl, 2-formylaminonaphthalene, 1-formylaminonaphthalene, and 2-acetylaminofluorene were deacylated by formamidase purified from rat liver cytosol. Formamidase catalyzed both Nformylation of arylamines, and deacylation of N-arylformamides and N-arylacetamides.

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Some historical aspects of N-aryl carcinogens and their metabolic activation.

Cited by 86 publications

References 59 publications

Formation and persistence of arylamine DNA adducts in vivo.

Formation and persistence of arylamine DNA adducts in vivo.

Deacylation of N-Formylanilines and N-Acetylanilines by Rat Liver Formamidase

Deacylation of N-Arylformamides andN-Arylacetamides by Formamidase in Rat Liver

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