Search PubMed⌕ Search

Biomedical subjects

M I Lerman

Publications and source records attributed to M I Lerman.

At least 163 records · Page 9Linked to original sources

Kpn I family of long interspersed repeated DNA sequences in primates: polymorphism of family members and evidence for transcription.

An approximately equal to 2-kilobase-pair-long member (Kpn I-LS1) of the African green monkey Kpn I family of repeated sequences has been cloned, subjected to sequence analysis, and compared to other family members which are over 6 kilobase pairs (Kpn I-alpha 7) and 829 base pairs (Kpn I-RET) long. Both Kpn I-LS1 and Kpn I-RET lack sequences found at the ends of the longer family member and their structures resemble those of processed genes. Kpm I-LS1 sequences are colinear with part of the long family member, Kpn I-alpha 7. However, although all sequences in Kpn I-RET are represented in Kpn I-LS1, the two are not colinear; Kpn I-RET is missing 731 base pairs found in Kpn I-LS1 and one segment flanking the deletion is inverted. The results demonstrate that Kpn I family members are not only of different lengths but may also contain scrambled arrangements of common sequences. Sequences in Kpn I-LS1 hybridize to RNA from monkey and human cells, indicating that some family members are transcribed.

Animals↗

Unusual class of Alu sequences containing a potential Z-DNA segment.

A potential Z-DNA sequence, (dA-dC)9, has been found to replace the customary A-rich region in the middle of an Alu family member in the African green monkey genome. This Alu, bounded by imperfect direct repeats, also contains an unusual 3' end and may be a member of a large subfamily of such sequences.

Animals↗

Membrane and genetic events in tumor promotion: studies with promoter resistant variants of JB6 cells.

The derivation and properties of JB6 mouse epidermal clonal cell lines are reviewed and the conclusions that can be drawn from studies with the JB6 mouse epidermal system are summarized. Promoter induced mitogenic stimulation, epidermal growth factor (EGF) receptor binding and stimulated hexose transport are apparently not required for promotion of neoplastic transformation in JB6 cells by phorbol esters and other promoters. Phorbol ester receptor binding (or protein kinase C activation) and switched-off collagen synthesis may be required but definitive proof is not available. Decreased cell surface ganglioside GT synthesis, elevated superoxide, and one or more genes that determine promotion sensitivity appear to distinguish sensitive from resistant cells and to be required for promotion of neoplastic transformation in JB6 cells. The hypothesis is proposed that GT is a target for reactive oxygen elevated by 12-O-tetradecanoylphorbol-13-acetate (TPA) exposure and that GT oxidation produces decreased GT net synthesis which in turn leads to promotion of transformation. Finally evidence is presented suggesting the involvement of at least two genes in transformation of JB6 cells by TPA, one in induction, the other in maintenance of transformation.

Animals↗

[Accelerated microsomal DNA synthesis under the influence of xenobiotics and chemical carcinogens].

Injection of 3,4-benz(a)pyrene, methyl nitrosourea and phenobarbital into healthy mice of the C3HA line results in a rapid, sharp increase of [14C]-thymidine incorporated into liver microsomal DNA, accompanied by a suppression of nuclear DNA synthesis. In the liver of neoplastic mice and in the ascite cells of hepatoma 22A the system of microsomal DNA synthesis was insensitive to the injection of methyl nitrosourea. Cycloheximide and puromycin, which strongly inhibited nuclear DNA synthesis, had no effect on the synthesis of microsomal DNA. Stimulation of [14C]-thymidine incorporation into microsomal DNA after injection of methyl nitrosourea and 3,4-benz(a)pyrene may be accounted for not only by an increase of the DNA reparation processes, since caffeine, the inhibitor of post-replicatory reparation of DNA, did not eliminate the induction of microsomal DNA synthesis in the liver. Hydroxyurea in combination with methyl nitrosourea and phenobarbital significantly suppressed the synthesis of nuclear DNA in the liver and did not affect the synthesis of mtDNA; the stimulating effects of these inducers on the synthesis of microsomal DNA was thereby removed. This is indicative of independence of synthesis of microsomal DNA on that of nuclear DNA and mtDNA. Different specific radioactivities of microsomal, nuclear and mtDNAs in the regenerating mouse liver on the 5th, 10th and 15th post-hepatectomy days may be due to different metabolic stability of these DNAs. A possible role of microsomal DNA as a xenobiotic system component is discussed.

Animals↗

Periodically interspersed repetitive sequences may govern higher-order DNA coiling in chromatin and chromosomes.

The interspersed periodic arrangement of repetitive and unique sequences in eukaryotic DNAs is proposed as the underlying molecular basis for higher-order DNA coiling in chromatin and mitotic chromosomes. It is assumed that (i) two types of interspersed repetitive sequences are distributed strictly periodically throughout the genome, splitting the single copy DNA into short and long periods respectively in such a pattern that each long period is composed of a definite number of short periods and repeats, (ii) the short and long periods make the turn lengths of the solenoid and supersolenoid structures respectively determining their diameters; (iii) specific proteins interact with each type of repeats making cross ties between nearby repeats of each class helping to form, constrain, and stabilize the solenoid and the supersolenoid structures: (iv) the long period may be equated with the basic chromomere unit. The model predicts: (i) splitting of contiguous genes by inserted repetitive sequences; and (ii) two types of genomes differing in the hierarchy of DNA coiling.

Animals↗

[Metabolic activation of N-methyl-N-nitrosourea in normal and tumor cells].

N-methyl-N-nitrosourea is metabolised by mouse liver microsomes yielding highly reactive product(s) capable of alkylating cellular macromolecules. Based on cofactor requirement (NADPH, oxygen), inhibition (NaN3) and induction by phenobarbital, 3,4-benz(a)pyrene, and MNU, the reaction is cytochrome P-450-dependent. Analysis of the kinetics and dose dependence of alkylation in vivo and in tissue homogenates confirms the fact that MNU must undergo metabolic activation in vivo.

Alkylating Agents↗

[Albumin mRNA from rat liver cells. Analysis of immunoadsorption of individual polyribosomes].

The analysis of albumin polyribosomes immunoadsorption is carried out using "sandwich" immunoadsorbents prepared on the basis of two aminobenzylcelluloses: commercial (paraaminobenzylcellulose) and synthesised (methaaminobenzyloxymethylcellulose). A method is worked out which is good for the estimation of the adaptibility of different aminobenzylcellulose preparations as an insoluble basis for the immunoadsorbent. Major properties of the "sandwich" sorbent (the accessible capacity and specificity) and the percent of isolated individual polyribosomes are found to be interrelated and determined by conditions of the immunoadsorption reaction. The increase of polyribosomes and sorbent concentrations and their ratio in the incubation medium results in the increase of the sorbent accessible capacity and the decrease in the inspecific adsorption but at the same time the percent of adsorbed polyribosomes decrease too. The "excess" of adsorbent with respect to polyribosomes, participating in the binding reaction, is necessary for the quantitative isolation of individual polyribosomes.

Albumins↗

Stimulation of growth of connective tissue by low-molecular-weight constituents from rapidly growing tissues.

The effect of low-molecular-weight cell constituents from regenerating liver and granulation tissue on the growth of the connective tissue during skin wound healing has been investigated. Repeated injections (intravenous or subcutaneous) of these compounds greatly accelerated the growth of connective tissue by stimulation of both fibroblast proliferation and collagen biogenesis and thus promoted wound healing. These results suggest that the low-molecular-weight cell constituents from dividing cells contain internal factor(s) capable of committing resting cells to D.N.A. synthesis and division or of accelerating D.N.A. synthesis in committed cells.

Animals↗

Metabolic heterogeneity of nuclear poly (A)-containing RNA in mouse liver.

The analysis by the approach to equilibrium labeling method has shown that the poly(A)+ fraction of liver hnRNA is not a uniform class of molecules, but is comprised of two distinct subclasses with half-lives of 5 and 60 min, while the poly(A)- hnRNA was metabolically homogeneous and turned over with a rather uniform half-life of 30 min. The results suggest that (a) poly(A) synthesis and addition is not limiting for the rate of hnRNA processing, and (b) there is a correlation between the kinetics of mRNA appearance in the cytoplasm and kinetic behavior of their possible nuclear precursors.

Animals↗

[Metabolism of N-methyl-N-nitrosourea in various mouse tissues under inhibition of protein and nucleic acid synthesis].

The contribution of C1-pool and antimetabolite utilization to modification (labeling) of macromolecules of various mouse tissues after a single injection of 1-14C-methylnitrosourea was studied, using inhibitors of protein and nucleic acid synthesis. It was shown that about 50% of radioactivity found in the proteins, lipoproteins and DNA (but not in RNA) might be supplied by the C1-pool and/or through utilization of radioactive metabolites in the first 3-6 hours following the injection of 1-14C-methylnitrosourea. The data obtained allow to evaluete the degree of alkylation of macromolecules in various organs and tissues.

Animals↗