Modifications of ribonucleic acid by chemical carcinogens. II. In vivo reaction of N-2-acetylaminofluorene with rat liver ribonucleic acid

Biochemistry ◽  
1970 ◽  
Vol 9 (3) ◽  
pp. 503-508 ◽  
Author(s):  
Manjul K. Agarwal ◽  
I. Bernard Weinstein
1975 ◽  
Vol 152 (1) ◽  
pp. 51-56 ◽  
Author(s):  
B M Mullock ◽  
R H Hinton

To assess the contribution made by mRNA-containing particles to the heterogeneity previously observed among rat liver 40S ribonucleoprotein particles, the amount of poly(A)-containing RNA in subribosomal particles was determined. RNA was labelled with orotate in vivo for 24h and then for 50min. Poly(A)-containing RNA was trapped on filters impregnated with poly(U). Very little poly(A)-containing RNA was found in conventionally prepared ribonucleoprotein particles after fractionation in sucrose. However, after preparation of ribonucleoprotein particles by sedimentation through 1 M-sucrose in the presence of 0.15M-KCl or by precipitation with Mg2+ as described by Leitin & Lerman [(1969) Biokhimiya 34, 839-849], amounts of poly(A)-containing RNA were similar to amounts of mRNA found by other workers in total ribonucleoprotein particles. Even in such preparations, less than 5% of the total rapidly labelled RNA in native subribosomal-particle fractions was mRNA. It seems that mRNA-containing particles make up only a very small part of the population of subribosomal particles in liver.


1972 ◽  
Vol 128 (1) ◽  
pp. 59-68 ◽  
Author(s):  
A. E. Pegg

1. The ethylated nucleosides present in tRNA isolated from the livers of rats treated with 0.5g of l-ethionine/kg body wt. were investigated. Evidence that this tRNA contained N2-ethylguanine, N2N2-diethylguanine, N2-ethyl-N2-methylguanine, 7-ethylguanine, two ethylated pyrimidines and ethylated ribose groups was obtained. 2. Ethylation of bacterial tRNA was catalysed by extracts containing tRNA methylases prepared from rat liver by using S-adenosyl-l-ethionine as an ethyl donor, but the rate of ethylation was 20 times less than the rate of methylation with S-adenosyl-l-methionine as a methyl donor. 3. The principal product of such ethylation in vitro was N2-ethylguanine and traces of the other ethylated guanines and pyrimidines found in tRNA isolated from rats treated with ethionine in vivo were also found. 1-Ethyladenine was not formed, although 1-methyl-adenine is a major product of methylation of bacterial tRNA by these extracts, and 1-ethyladenine was not present in the rat liver tRNA isolated from ethionine-treated animals. 4. After injection of actinomycin D (15mg/kg body wt.) or l-methionine (1.0g/kg body wt.) before the ethionine, ethylation of tRNA was diminished by about 80% but not completely abolished. Administration of 1-aminocyclopentanecarboxylic acid (2.5g/kg body wt.) to inhibit the formation of S-adenosyl-l-ethionine inhibited ethylation of tRNA by 44%. 5. These results suggest that not all of the ethylation of tRNA that occurs in the livers of rats treated with ethionine is mediated by the action of tRNA methylases acting with S-adenosyl-l-ethionine as a substrate, but that this pathway does occur and accounts for a major part of the observed ethylation. 6. The results are discussed with reference to ethionine-induced hepatocarcinogenesis.


1972 ◽  
Vol 129 (3) ◽  
pp. 519-528 ◽  
Author(s):  
P. J. O'Connor ◽  
M. J. Capps ◽  
A. W. Craig ◽  
P. D. Lawley ◽  
S. A. Shah

1. rRNA was isolated from rat liver at short intervals after the intraperitoneal injection of [14C]methyl methanesulphonate (50mg/kg) or NN-di[14C]methylnitrosamine (2mg/kg). These doses were chosen to minimize the effects of toxicity. 2. The following methods of hydrolysis of [14C]methylated rRNA were employed: enzymic digestion to nucleosides at pH8; alkaline hydrolysis and conversion into nucleosides; acid hydrolysis to bases. 3. The methylation products were analysed by chromatography on columns of Dowex-50 (H+ form) and Dowex-50 (NH4+ form). 4. With both methylating agents the principal product of methylation was 7-methylguanine. Differences were obtained, however, in the molar proportions of the minor bases 3-methylcytosine, 1-methyladenine and 7-methyladenine. Methylation at the O-6 position of guanine was a significant feature of rRNA obtained from the NN-di[14C]methylnitrosamine-treated animals but was not detected in rRNA after treatment with [14C]methyl methanesulphonate.


1973 ◽  
Vol 136 (1) ◽  
pp. 209-215 ◽  
Author(s):  
Hajime Nawata ◽  
Kenichi Kato

1. Administration of 3,5-dicarbethoxy-1,4-dihydrocollidine to rats caused a marked increase in the activity of δ-aminolaevulinic acid synthetase as well as a slight net increase in RNA in the livers. 2. 3,5-Dicarbethoxy-1,4-dihydrocollidine primarily stimulated the synthesis of RNA in the nucleus of the liver cell. 3. The decrease in RNA synthesis after administration of this drug resulted in a rapid decrease in the activity of this induced enzyme. This was also confirmed by treatment with actinomycin D. 4. From kinetic experiments on synthesis of RNA and δ-aminolaevulinic acid synthetase in vivo the induction mechanism of this enzyme was discussed.


1989 ◽  
Vol 163 (3) ◽  
pp. 1412-1417
Author(s):  
D. Kanduc ◽  
A. Aresta ◽  
M.R. Rossiello ◽  
T. Ranieri ◽  
E. Quagliariello

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