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The covalent binding of metabolites of dimethylaminoazobenzene, β‐naphthylamine and aniline to nucleic acids in vivo
Author(s) -
Roberts J. J.,
Warwick G. P.
Publication year - 1966
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910010207
Subject(s) - nucleic acid , rna , biochemistry , dna , microbiology and biotechnology , nucleotide , orotic acid , biology , chemistry , gene
Abstract1. Following injection of dimethylaminoazobenzene‐ 3 H labelled in the primed ring (150 mg/kg) into male albino rats and guinea‐pigs maintained on a diet containing 10% protein, radioactivity was covalently bound to r‐RNA, DNA, cytoplasmic protein and nuclear protein of liver and spleen. 2. For liver the maximum levels of binding (μM/g × 10 2 ) were r‐RNA 11.4, cytoplasmic protein 54, nuclear protein 39, DNA 1.4; for spleen: r‐RNA 1.0, DNA 0.5, cytoplasmic protein 89, and nuclear protein 39; and for guinea‐pig liver r‐RNA 3.4, DNA 2.2, cytoplasmic protein 55, nuclear protein 28, indicating a much higher ratio of protein binding to r‐RNA binding than in the rat (16 compared with 5). The difference in ratio was also large for the binding to two transplanted hepatomas in August and Hooded rats compared with albino rat liver (37 and 13). 3. For rat liver r‐RNA and protein the decay of radioactivity paralleled the rate of turnover of r‐RNA (as measured by orotic acid‐ 3 H incorporation) and of protein. The level of DNA‐bound radioactivity remained constant for 290 hours. 4. The radioactivity associated with the nucleic acids and proteins remained bound after treatment with 0.3 N KOH which converts the nucleic acids to nucleotides, and with Crotalus adamanteus venom which converts them to purine and pyrimidine nucleosides. Treatment with N HCl for 1 hr at 100°C which forms purine bases and pyrimidine nucleotides and degrades proteins into peptides and amino acids, liberated the majority of the radioactivity so that it became extractable at various pH values. 5. The binding of β‐naphthylamine‐ 3 H and aniline‐ 3 H hydrochloride to rat liver, spleen and kidney were also studied. Binding occurred to DNA, ribosomal RNA and protein in each case. For β‐naphthylamine the levels of metabolite binding were similar to dimethylaminoazobenzene metabolite binding to guinea‐pig liver components. For aniline hydrochloride, binding to ribosomal RNA and protein was of a low order. 6. The possible relevance of these findings to the problem of carcinogenesis is discussed.