Abstract
Aromatic compounds that have nitrogen atoms attached to their ring carbons have a potential for eliciting a variety of adverse cytotoxic, mutagenic and carcinogenic responses. The actual biological effects produced by these agents are dependent on their structure, the ability of the host organism to metabolize the compound and the response of the organism to the metabolites that are generated. Although this group of compounds is most often referred to as aromatic amines, the term N-substituted aromatic compounds is more appropriate since it is sufficiently broad to include both nitrocompounds that may be converted metabolically to aromatic amines, as well as metabolites of amines, e.g. hydroxamates, amides and nitroso derivatives, that have quite different chemical properties. This report is intended to provide insight into the carcinogenic potential of these compounds and the mechanisms by which they are believed to effect this activity.
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References
Bartsch, H. and Hecker, E., 1971, On the metabolic activation of N-hydroxy-N-2-acetylaminoflourene. III. Oxidation with horseradish peroxidase to yield 2-nitrosofluorene and N-acetoxy-N-2-acetylaminofluorene, Biochim. Biophys. Acta., 237: 567–578.
Bartsch, H., Dworkin, M., Miller, J.A., and Miller, E.C., 1972, Electrophilic N-acetoxyaminoarenes derived from carcinogenic N-hydroxy-N-acetylaminoarenes by enzymatic deacetylation and transacetylation in liver, Biochim. Biophys. Acta., 286: 272–298.
Bartsch, H., Dworkin, C., Miller, E.C., and Miller, J.A., 1973, Formation of electrophilic N-acetoxyarylamines in cytosols from rat mammary gland and other tissues by transacetylation from the carcinogen N-hydroxy-2-acetylaminobiphenyl, Biochim. Biophys. Acta., 304: 42–55.
Bengtsson, U., Johansson, S., and Angervall, L., 1978, Malignancies of the urinary tract and their relation to analgesic abuse, Kidney Internatl., 13: 107–113.
Bhanot, 0.S., Khan, S.A., and Chambers, R.W, 1979, A new system for studying molecular mechanisms of mutation by carcinogens, J. Biol. Chem., 254: 12684–12693.
Cardona, R.A. and King, C.M., 1976, Activation of the 0-glucuronide of the carcinogen N-hydroxy-2-fluorenylacetamide by enzymatic deacetylation in vitro: formation of fluorenylamine–tRNA adducts, Biochem. Pharmacol., 25: 1051–1056.
Clayson, D.B., and Garner, R.C., 1976, Carcinogenic aromatic amines and related compounds, in: “Chemical Carcinogens,” C.E. Searle, ed., American Chemical Society, Washington, D.C
Claxton, L. and Husingh, J., 1980, Characterization of the mutagens associated with diesel particle emissions, 11th Annual Meeting Environmental Mutagen Society, March 16–19, p. 54.
Coogan, P.S., H.T. Maganini, J.J. Newton, Jr., and G.M. Hass, 1978, Progesterone inhibition of 2-AAF induction of urogenital tumors in rabbits, Lab. Investigations, 38: 339.
Cramer, J.W., Miller, J.A., and Miller, E.C., 1960, N-Hydroxylation: a new metabolic reaction observed in the rat with the carcinogen 2-acetylaminofluorene, J. Biol. Chem., 235: 885–888.
DeBaun, J.R., Miller, E.C., and Miller, J.A., 1970, N-Hydroxy-2-acetylaminofluorene sulfotransferase: its probable role in carcinogenesis and in protein-(methionS-yl) binding in rat liver, Cancer Res., 30: 577–595.
Epler, J.L., Rao, T.K., and Larimer, F.W., 1980, Isolation and identification of mutagenic polycyclic aromatic amines in synthetic crude oils. 11th Annual Meeting, Environmental Mutagen Society, March 16–19, p. 54.
Glowinski, I.B., Weber, W.W., Fysh, J.M., Vaught, J.B., and King, C.M., 1980, Evidence that arylhydroxamic acid N,0-acyltransferase and the genetically polymorphic N-acetyltransferase are properties of the same enzyme in rabbit liver, J. Biol. Chem., 255: 7883–7890.
Glowinski, I.B., Savage, L., King, C.M., 1981, Relationship between metabolic activation and deacylation of arylhydroxamic acids by liver microsomes of several species, Proc. Am. Can Res., 22: 102.
Gutmann, H.R., Malejka-Giganti, D., Barry, E.J., and Rydell, R.E, 1972, On the correlation between the hepatocarcinogenicity of the carcinogen, N-2-fluorenylacetamide, and its metabolic activation by the rat, Cancer Res., 31: 1554–1561.
Hoffman, D. and Wynder, E.L., 1976, Environmental respiratory carcinogenesis, in: “Chemical Carcinogens, ACS Monograph 173,” C.E. Searle, ed., American Chemical Society, Washington, D.C.
Howard, P.C., Casciano, D.A., Beland, F.A., and Shaddock, J.G., Jr., 1981, The binding of N-hydroxy-2-acetylaminofluorene to DNA and repair of the adducts in primary rat hepatocyte cultures, Carcinogenesis., 2: 97–102.
Irving, C.C., 1966, Enzymatic deacetylation of N-hydroxy-2acetylaminofluorene by liver microsomes, Cancer Res., 26: 1390–1396.
Irving, C.C., 1979, Species and tissue variations in the metabolic activation of aromatic amines, in: “Carcinogens: Identification and Mechanisms of Action,” Griffin, A.C. and Shaw, C.R., eds., Raven Press, New York.
Irving, C.C., Janss, D.H., and Russell, L.T., 1971, Lack of N-hydroxy-2-acetylaminofluorene sulfotransferase activity in the mammary gland and Zymbal’s gland of the rat, Cancer Res., 31: 387–391.
Irving, C..C., Wiseman, R., Jr., and Hill, J.T., 1967a, Biliary excretion of the 0–glucuronide of N–hydroxy2–acetylaminofluorene by the rat and rabbit, Can Res., 27–2309–2317.
Jarvinen, M., Santti, R.S.S., Hopsu-Havu, V.K., 1979 Partial purification and characterization of two enzymes from guinea pig liver microsomes that hydrolyze carcinogenic amides, 2-acetylaminofluorene and N-hydroxy-2-acetylaminofluorene, Biochem. Pharm., 20: 2971–2982.
Kadlubar, F.F., Unruh, L.E., Beland, F.A., Straub, K.M., and Evans, F.A., 1980, In vitro reaction of the carcinogen, N-hydroxy-2-naphthyamine, with DNA at the C-8 and N2 atoms of guanine and at the N6atom of adenine, Carcinogenesis, 1: 139–150.
King, C.M., Allaben, W.T., 1980, Arylhydroxamic acid acyltransferase, in: “Enzymatic Basis of Detoxication, Vol. II,” W. Jakoby, ed., Academic Press, Inc.
King, C.M., and Kriek, E., 1965, The differential reactivity of the oxidation products of o-aminophenols towards protein and nucleic acid. Biochim. Biophys. Acta., 111: 147–153.
King, C.M., and Phillips, B. 1968, Enzyme-catalyzed reactions of the carcinogen N-hydroxy-2-fluorenylacetamide with nucleic acid. Science, 159: 1351–1353.
King, C.M., and Phillips, B., 1969, N-Hydroxy-2-fluorenylacetamide. Reaction of carcinogen with guanosine, ribonucleic acid, deoxyribonucleic acid, and protein following enzymatic deacetylation or esterification, J. Biol. Chem., 244.
King, C.M., Traub, N.R., Cardona, R.A., and Howard, R.B., 1976, Comparative adduct formation of 4-aminobiphenyl and 2-aminofluorene derivatives with macromolecules of isolated liver parenchymal cells, Can. Res., 36: 2374–2381.
King, C.M., Traub, N.R., Lortz, Z.M.,and Thissen, M.R., 1979, Metabolic activation of arylhydroxamic acids by N-O-acyltransferase of rat mammary gland, Can Res., 3369–3372.
Kosuge, T., Tsuji, K., Wakabayashi, K., Okamoto, T., Shudo, K., Iitaka, Y., Itai, A., Sugimura, T., Kawachi, T., Nagao, M., Yahagi, T., and Seino, Y., 1978, Isolation and structural studies of mutagenic principles in amino acid pyrolysates, Chem. Pharm. Bull., 26: 611–619.
Kriek, E., 1965 On the interaction of N-2-fluorenylhydroxylamine with nucleic acids in vitro. Biochem. Biophys. Res. Commun., 20: 793–799.
Kriek, E., Miller, J.A., Juhl, U., and Miller, E.C., 1967, 8-(N-2-Fluorenylacetamido)guanosine, an arylamidation reaction product of guanosine and the carcinogen N-acetoxy-N-2-fluorenylacetamide in neutral solution, Biochemistry, 6: 177.
Kriek, E., and Westra, J.G., 1979, Metabolic activation of aromatic amines and amides and interactions with nucleic acids, in: “Chemical Carcinogens and DNA, Vol. II,” Grover, P.L., ed., CRC Press, Inc., Boca Raton, FA.
Lee, M.S., and King, C.M., 1981, New syntheses of N-(guanosin-8-yl)-4-aminobiphenyl and its 5’-monophosphate, Chem. Biol. Interactions, 34: 239–248.
Lofroth, G., 1978, Mutagenicity assay of combustion emissions, Chemosphere, 7: 791–798.
Maher, V.M., Miller, E.C., Miller, J.A., and Szybalski, W., 1968, Mutations and decreases in density of transforming DNA produced by derivatives of the carcinogens 2-acetylaminofluorene and N-methyl-4-aminoazobenzene, Mol. Pharm, 4: 411–426.
Malejka-Giganti, D., and Gutmann, H.R., 1975, N-Hydroxy-2fluorenylacetamide, an active intermediate of the mammary carcinogen N-hydroxy-2-fluorenylbenzenesulfonamide (38980), Proc. Soc. Expl. Biol. Med., 150: 92–97.
Mermelstein, R., Kariazides, D.K., Butler, M., McCoy, E.C., and Rosenkranz, H.S., 1981, The extraordinary mutagenicity of nitropyrenes in bacteria, Mutation Res, 89: 187–196.
Miller, E.C., 1978, Some current perspectives on chemical carcinogenesis in humans and experimental animals: presidential address, Cancer Res., 38: 1479–1496.
Miller, E.C., Miller, J.A.., and Hartman, H.A., 1961, N-hydroxy-2-acetylaminofluorene: A metabolite of 2-acetylaminfluorene with increased carcinogenic activity in the rat, Cancer Res., 31: 815–824.
Moore, P., and Strauss, B.S., 1979, Sites of inhibition of in vitro DNA synthesis in carcinogen-and UV-treated clo X174 DNA, Nature, 278: 664–666.
Morton, K.C., Wang, C.Y., Garner, C.D., and Shirai, T., 1981, Carcinogenicity of benzidine, N,N’-diacetylbenzidine, and N-hydroxy-N-N’-diacetylbenzidine for female CD rats, Carcinogenesis, 2: 747–752.
National Cancer Institute, 1978a Bioassay of aniline hydrochloride for possible carcinogenicity, CAS No. 142–04–1, NIC–CG–TR–130.
National Cancer Institute, 1978b Bioassay of o–Anisidine hydrochloride for possible carcinogenicity, CAS NO. 134–29–0, NCI–CG–TR–89.
Neumann, H.G., 1980, On the significance of metabolic activation and binding to nucleic acids of aminostilbene derivatives in vivo, Natl. Cancer Inst. Monogr., in press.
Parkes, H.G., 1976, “The epidemiology of the aromatic amine cancers in: Chemical carcinogens, C.E. Searle, ed., Am. Chem. Soc., Washington, D.C.
Pitts, J.A., Jr., Van Cauwenberghe, K.S., Grosjean, D., Schmid, J.P., Fitz, D.R., Belser, W.L., Jr., Knudson, G.B., and Hynds, P.M., 1978, Atmospheric reactions of polycyclic aromatic hydrocarbons: facile formation of mutagenic nitro derivatives, Science, 202: 515–519.
Scribner, D.L., and McCloskey, J.A., 1978, Deamination of 1-methylcytosine by the carcinogen N-acetoxy-4-acetamido stilbene: Implications for hydrocarbon carcinogenesis, J. of Organic Chem, 43: 2085.
Shirai, T., Fysh, J.M., Lee, M.S., Vaught, J.B.,and King, C.M., 1981a, N-hydroxy-N-acylarylamines: relationship of metabolic activation to biological response in the liver and mammary gland of the female CD rat, Cancer Res: 41: 4346–4353.
Shirai, T., and King, C.M., 1981b, Relationship of H-thymidine incorporation to the metabolic activation of arylhydroxamic acids by rat hepatocytes, Proc. Am Assoc. Can Res: 22: 99.
Shirai, T., Lee, M.S., Wang, C.Y., King, C.M., 1981c, Effects of partial hepatectomy and dietary phenobarbital on liver and mammary tumorigenesis by two N-hydroxy-N-acylaminobiphenyls in female CD rats, Cancer Res., 41: 2350–2456.
Thorgeirsson, S.S., Wirth, P.J., Nelson, W.L., and Lambert, G.H., 1977, Genetic regulation of metabolism and mutagenicity of 2-acetylaminofluorene and related compounds in mice, in: “Origins of Human Cancer,”Hiatt, Watson, Winsten, eds., Cold Spring Harbor, NY.
Vaught, J.B., Lee, M.S., Shayman, M.A., Thissen, M.R., and King, C.M, 1981, Arylhydroxylamine-induced ribonucleic acid chain cleavage and chromatographic analysis of arylamine ribonucleic acid adducts, Chem. Biol Interactions, 34: 109–124.
Wang, C.Y., Lee, M.S., King, C.M., and Warner, P.O., 1980, Evidence for nitroaromatics as direct-acting mutagens as airborne particulates, Chemosphere, 9: 83–87.
Weber, W.W., 1973, Acetylation of drugs, in: “Metabolic conjugation and metabolic hydrolysis”, W.H. Fishman, ed., Academic Press, New York.
Weeks, C.E., Allaben, W.T., Louie, S.C., Lazear, E.J., and King, C.M., 1978, Role of arylhydroxamic acid acyltransferase in the mutagenicity of N-hydroxy-N-2fluorenylacetamide in Salmonella typhimurium, Cancer Res., 38: 613–618.
Weeks, C.E., Allaben, W.T., Tresp, N.M., Louis, S.C., Lazear, E.J., and King, C.M., 1980, Effects of structure of N-acyl-N-2-fluorenylhyroxylamines on arylhydroxamic acid acyltransferase, sulfotransferase and deacylase activities, and on mutations in Salmonella Typhimurium TA 1538, Cancer Res., 40: 1204–1211.
Wirth, P.J., and Thorgeirsson, S.S., 1980, Mechanism of N-hydroxy-2-acetylaminofluorene mutagenicity in the Salmonella test system, role of N-O-acyltransferase and sulfotransferase from rat liver, Mol. Pharm: 19: 337–344.
Wu, S-C.G., and Straub, K.D., 1976,. Purification and characterization of N-hydroxy-2-acetylaminofluorene sulfotransferase from rat liver, J. Biol. Chem., 251: 6529–6536.
Zavon, M.R., Hoegg, R., and Bingham, E., 1973, Benzidine exposure as a cause of bladder tumors, Arch. Environ. Health, 27: 1–7.
Zenser, T.V., Mattammal, M.B., Armbrecht, H.J., and Davis, B.B., 1980, Benzidine binding to nucleic acids mediated by the peroxidative activity of prostaglandin endoperoxide synthetase, Can Res., 40: 2839–2845.
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King, C.M. (1982). N-Substituted Aromatic Compounds. In: Nicolini, C. (eds) Chemical Carcinogenesis. NATO Advanced Study Institutes Series, vol 52. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-4334-9_2
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DOI: https://doi.org/10.1007/978-1-4684-4334-9_2
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