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Biomedical subjects

S J Kerr

Publications and source records attributed to S J Kerr.

14 recordsLinked to original sources
PubMed1990

Methylated oxypurines and induction of differentiation of murine erythroleukemia cells.

Murine erythroleukemia cell lines derived from Friend virus infected mice can be induced to differentiate in vitro by numerous agents. Among these compounds are certain naturally occurring purines such as hypoxanthine or 1-methylhypoxanthine. We have extended these studies to other modified oxypurines and have identified some areas of cell regulation with which they may be interacting. Monomethylated derivatives of guanine, hypoxanthine or xanthine are active as inducers of differentiation. Excluding hypoxanthine, the parent oxypurines guanine and xanthine are ineffective in inducing differentiation. The dimethyl- and trimethylxanthine derivatives are also inactive as inducers. The methylated oxypurines are not metabolized to nucleotides by the cell and, therefore, probably do not interact with nucleic acid synthesis directly. We have investigated one cellular process of possible regulatory significance with which they do interact. ADP-ribosylation has been implicated in control of gene expression and differentiation. The methylated oxypurines inhibit this reaction, as measured in permeabilized cells, in the same concentration range at which they are effective as inducers of differentiation. Additionally, 1-methylguanine and 7-methylguanine decrease incorporation of mannose and glucosamine into glycoprotein and into dolichol-oligosaccharide precursors. These effects may be related to cell surface alterations observed during differentiation.

Adenosine Diphosphate↗
PubMed1985

Induction of adipocyte formation in 10T1/2 cells by 1-methylguanine and 7-methylguanine.

1-Methylguanine and 7-methylguanine are naturally occurring modified purines derived from tRNA, found in elevated levels in the serum and urine of cancer patients. When C3H/10T1/2 clone-8 mouse cells are exposed to low levels of the methylated purines, they are induced to differentiate into adipocytes. Differentiation is induced in a dose-dependent manner and is similar in extent to that achieved by other inducing agents, such as 5-azacytidine. The methylated purines are not mutagenic, nor are they incorporated into DNA. They may exert their effect by modifying cellular regulatory processes, such as methylation of DNA. High levels of circulating methylated purines in cancer patients may play a role in tumor-host interactions.

Adipose Tissue↗
PubMed1979

Selective changes in tRNA methyltransferase activity in confluent monolayers of WI-38 cells stimulated to proliferate.

In quiescent confluent monolayers of WI-38 cells, the specific activity of the tRNA methyltransferases falls to 20% of the level found in log phase cells. When the resting cells are stimulated to proliferate by a change to fresh medium, the enzyme show a rapid rise in specific activity which correlates with early increases in the rate of tRNA synthesis. The specific activity of the enzymes continues to rise throughout the period of DNA synthesis, at the end of which it is somewhat higher than that of log phase cells. The increases in enzyme activity could be blocked by exposure of the stimulated cells to Actinomycin D (2 microgram/ml). The increases in activity were not equivalent for the different base-specific enzymes. The contribution of the N2-methylguanine specific enzyme remained relatively constant, while that of the N2,N2-dimethyl-guanine specific and 1-methyladenine specific enzymes doubled and tripled, respectively, by late S phase. The contributions of the 1-methylguanine and the 7-methylguanine specific enzymes fell to a few percent of the total by late S phase. This indicates non-coordinate variations in the expression of the different base-specific enzymes after stimulation of resting cells and may be related to altered isoaccepting tRNA profiles observed in resting and growing cells.

Cell Division↗
PubMed1979

Karyotype and tumorigenicity of 1-methylguanine-transformed Chinese hamster cells.

Chinese hamster embryo cells transformed with the tRNA catabolite 1-methylguanine were characterized by Giemsa-banded karyotyping and by their tumorigenic potency in athymic nude mice. All seven 1-methylguanine-transformed cell lines were hyperdiploid with a modal chromosome number of 23. Three of these lines had an additional marker chromosome derived from the long (q) arm of chromosome no. 4, and they had alterations of chromosome no. 5 as well. Two of these three cell lines were tumorigenic. Nonrandom chromosome changes were observed in the other four 1-methylguanine-transformed cell lines, which included the addition of all or a portion of chromosome no. 6. One of these cell lines was also tumorigenic in nude mice, Specific cytogenetic changes were observed in most 1-methylguanine-transformed populations in contrast to the karyotypic heterogeneity of a benzo[a]pyrene-transformed cell line.

Animals↗
PubMed1978

Altered growth properties of Chinese hamster cells exposed to 1-methylguanine and 7-methylguanine.

Primary Chinese hamster embryo cell cultures generally yield cell lines with a finite lifetime in culture. However, if early-passage cells are exposed chronically to either of two normal degradation products of transfer RNA, 1-methylguanine or 7-methylguanine, they are converted to continuous lines with altered growth characteristics and morphology. The continuous cell lines have saturation densities 2- to 10-fold higher than did finite control cultures, and some have the ability to grow in soft agar. Certain cultures have the general appearance of fibroblasts while others are more epithelial-like. Quantitative and qualitative alterations in the transfer RNA methyltransferases are early markers for neoplastic transformation in vivo and in vitro. Transfer RNA methyltransferase activity in the continuous lines is elevated compared to that of finite Chinese hamster cells. Neoplastic transformation has been demonstrated for a 1-methylguanine-derived line, and both 1-methylguanine- and 7-methylguanine-treated cell lines exhibit characteristics similar to those of Chinese hamster cells transformed with the carcinogen 3,4-benzopyrene or the DNA tumor virus SV40.

Animals↗
PubMed1975

Transfer of the methyl group of methionine to choline and to tRNA in the honeybee Apis mellifica L.

Contrary to some previous reports on the absence of biological transmethylation reactions in some insect species, the transfer of the methyl group of methionine-methyl 14C leading to choline and to methylated bases in tRNA was shown in the honeybee Apis mellifica. The addition of antibiotics to the food of the insect does not diminish the incorporation of radioactivity, proving that intestinal bacteria are not responsible for the methylation reactions observed.

Animals↗
PubMed1975

Alteration of glycine N-methyltransferase activity in fetal, adult, and tumor tissues.

Glycine N-methyltransferase activity has been examined in a number of fetal and adult organs, as well as in several rodent hepatomas, using both enzymatic and immunological techniques. In fetal rabbit liver, the activity first appears at a low level at about 20 days postfertilization and rises to high levels after birth, reaching maximum in the adult liver. In fast-growing hepatomas, the activity could not be detected by either enzymatic or immunological assay. It could be detected in the slower-growing hepatomas, but in considerably diminished levels compared with that of normal adult rat liver. Immunoassays gave no evidence for inactive forms of the enzyme in the tissues that had no enzymatic activity. Transfer RNA methyltransferase assays carried out simultaneously showed an inverse relationship to the glycine N-methyltransferase activity. The levels of transfer RNA methyltransferase activity were high in fetal and tumor tissues and lower in normal adult tissues.

Animals↗
PubMed1975

Interaction of normal and tumor transfer RNA methyltransferases with ethionine-induced methyl-deficient rat liver transfer RNA.

The tRNA methyltransferases from normal rat liver and Novikoff hepatoma have been compared with respect to their base specificity, capacity to methylate, and reaction kinetics, using mixed Escherichia coli B transfer RNA (tRNA) and ethionine-induced partially methyl-deficient rat liver tRNA. The pattern of base methylation of the two substrates is different with the use of enzymes from either source. In particular, N1-methylguanine methylation is much greater in the methyl-deficient rat liver tRNA. The enzymes from the two sources also show differences in specificity of base methylation in either substrate, particularly in the percentage of N2-methylguanine synthesized. The Novikoff hepatoma enzymes have a greater capacity for methylation with either type of tRNA than do rat liver enzymes. The methyl-deficient rat liver tRNA is a poorer substrate for the enzymes from both sources than is E. coli B tRNA in terms of rate of methylation as well as total acceptance of methyl groups. The affinity constants are somewhat higher for the methyl-deficient rat liver tRNA than for E. coli B tRNA. The Novikoff hepatoma enzymes, in general, have larger affinity constants than the rat liver enzymes. Maximal velocities for the various base-specific enzymes are lower with the methyl-deficient rat liver tRNA, with the exception of the 1-methylguanine specific enzymes. These enzymes from either rat liver or Novikoff hepatoma exhibit approximately a 2.5-fold greater maximal velocity with methyl-deficient rat liver tRNA.

Animals↗