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Translation of globin messenger RNA modified by benzo(a)pyrene 7,8-dihydrodiol 9,10-oxide in a wheat germ cell-free system

Journal Article · · J. Biol. Chem.; (United States)
OSTI ID:5432293
; ;
Poly(U/sub 3/G) and rabbit globin mRNA were modified with the active carcinogenic metabolite of benzo(a)pyrene, (+-)-7..beta..,8..cap alpha..-dihydroxy-9..cap alpha..,10..cap alpha..-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene, and the effects of modification on translation in a cell-free protein synthesizing system were studied. High performance liquid chromatography of modified nucleosides from enzymatically hydrolyzed globin mRNA reveals that the active carcinogen formed two adducts with guanosine, four adducts with adenosine, and one adduct probably with cytidine residues. When globin mRNA with 0.4 carcinogen residues/molecule is used as a template, incorporation of amino acids into proteins is inhibited by 50%, and mRNA with 2.4 residues has only 10% of the template activity compared to unmodified molecules. On the other hand, modification of poly(U/sub 3/G) has no effect on its template activity. Since no significant formation of smaller peptides in the protein synthesizing system programmed with modified mRNA is detected, it is suggested that the carcinogen does not block the elongation step in mRNA translation. However, glycerol gradient centrifugation of initiation complexes reveals that modified globin mRNA does not form initiation complexes with ribosomes as effectively as does the unmodified globin mRNA. These results suggest that modification significantly reduces the ability of mRNA to be translated by affecting the initiation step in protein synthesis.
Research Organization:
Columbia Univ. College of Physicians and Surgeons, New York, NY
OSTI ID:
5432293
Journal Information:
J. Biol. Chem.; (United States), Journal Name: J. Biol. Chem.; (United States) Vol. 255:2; ISSN JBCHA
Country of Publication:
United States
Language:
English

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Related Subjects

550201 -- Biochemistry-- Tracer Techniques
560305* -- Chemicals Metabolism & Toxicology-- Vertebrates-- (-1987)
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ADENOSINE
AMINO ACIDS
ANIMALS
AROMATICS
AZINES
BENZOPYRENE
BIOSYNTHESIS
CARBOXYLIC ACIDS
CONDENSED AROMATICS
CYTIDINE
DNA
GLOBIN
GUANOSINE
HETEROCYCLIC COMPOUNDS
HYDROCARBONS
INHIBITION
MAMMALS
MESSENGER-RNA
METABOLITES
NUCLEIC ACIDS
NUCLEOSIDES
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
PURINES
PYRIMIDINES
RABBITS
RIBOSIDES
RNA
SYNTHESIS
TOXICITY
VERTEBRATES