Modulation of the mutagenicity of three dinitropyrene isomers in vitro by rat-liver S9, cytosolic, and microsomal fractions following chronic ethanol ingestion

https://doi.org/10.1016/0165-1218(92)90246-VGet rights and content

Abstract

The effects of chronic ethanol feeding of rats on the ability of liver fractions to modulate the bacterial mutagenicity of three dinitropyrene isomers (1,3-, 1,6- and 1,8-DNP), which require bacterial enzymes but not an exogenous enzyme source for activation, were studied. The mutagenicity of the DNP isomers toward S. typhimurium TA98 and TA100 was attenuated in the presence of post-mitochondrial supernatants (S9) from both ethanol-fed and pair-fed rats albeit, that from the ethanol-fed group was more efficient in lowering the mutagenicity. The cytosolic fraction from ethanol-fed rats enhanced the mutagenicity of all of the DNP isomers in TA100. The most notable enhancement was with 1,3-DNP in which a more than 4-fold enhancement was obtained. Cytosol from pair-fed rats enhanced only the mutagenicity of 1,3-DNP, this by 2.9-fold. Cytosolic NADPH-nitroreductase activity from ethanol-treated rats toward 1,6-, 1,8- and 1,3-DNP was increased 2.8-, 1.7- and 1.3-fold, respectively over pair-fed controls. Cytosolic NADH-nitroreductase from ethanol-fed rats was increased with 1,3-DNP (1.7-fold) and 1,8-DNP (1.4-fold) as substrates, but not with 1,6-DNP. Microsomes decreased the mutagenicity of DNP similarly to S9, i.e., fractions from ethanol-fed rats were more efficient than those of pair-fed rats in deactivating all the DNP isomers. Per mg of protein, detoxification of DNP by S9 was more efficient than with microsomes, thus both cytosolic and microsomal enzymes are required for maximal detoxification. In summary, ethanol feeding modulates both the augmented cytosolic activation of DNP to mutagens and the deactivation of the direct-acting mutagenicity of DNP by microsomes. In combination, as is the case with S9, the microsomal detoxifying activity outcompetes the cytosolic activation.

References (50)

  • H.S. Rosenkranz et al.

    Mutagenicity and genotoxicity of nitroarenes: all nitro-containing chemicals were not created equal

    Mutation Res.

    (1983)
  • Y.Y. Tu et al.

    Pyrazole-induced cytochrome P-450 in rat-liver microsomes: an isozyme with high affinity for dimethylnitrosamine

    Biochem. Biophys. Res. Commun.

    (1981)
  • A. Abbondanza et al.

    Xanthine oxidase status in ethanol-intoxicated ratliver, Alcoholism

    Clin. Exp. Res.

    (1989)
  • P.J. Andrews et al.

    Identification of the DNA adducts formed by metabolism of 1,8-dinitropyrene in Salmonella typhimurium

    Carcinogenesis

    (1986)
  • F.A. Beland et al.

    Metabolic activation and DNA adducts of aromatic amines and nitroaromatic hydrocarbons

  • F.A. Beland et al.

    The in vitro metabolic activation of nitro polycyclic aromatic hydrocarbons

  • B. DeFlora et al.

    Influence of DT diaphorase on the mutagenicity of organic and inorganic compounds

    Carcinogenesis

    (1988)
  • Z. Djuric et al.

    Acetyl coenzyme A-dependent binding of carcinogenic and mutagenic dinitropyrenes to DNA

    Carcinogenesis

    (1985)
  • Z. Djuric et al.

    In vivo and in vitro formation of glutathione conjugates from the K-region epoxides of 1-nitropyrene

    Carcinogenesis

    (1987)
  • Z. Djuric et al.

    DNA binding of 1-nitropyrene and 1,6-dinitropyrene in vitro and in vivo: effects of nitroreductase induction

    Carcinogenesis

    (1988)
  • E.K. Fifer et al.

    Synthesis and mutagenicity of 1-nitro-6-nitrosopyrene and 1-nitro-8-nitrosopyrene, potential intermediates in the metabolic activation of 1,6- and 1,8-dinitropyrene

    Carcinogenesis

    (1986)
  • A.J. Garro et al.

    Enhancement of dimethylnitrosamine metabolism and activation to a mutagen following chronic ethanol consumption

    Cancer Res.

    (1981)
  • A.K.D. Hajos et al.

    DT-diaphorase-de-pendent nitroreduction of dinitropyrenes: Induction, stereoselectivity and mutagenicity

  • A.K.D. Hajos et al.

    Dinitropyrene nitroreductase activity of purified NAD(P)H:quinone oxidoreductase: role in rat-liver cytosol and induction by Aroclor-1254 pretreatment

    Carcinogenesis

    (1991)
  • A.K.D. Hajos et al.

    Purified NADPH quinone oxidoreductase enhances the mutagenicity of dinitropyrenes in vitro

    J. Biochem. Toxicol.

    (1991)
  • Cited by (0)

    View full text