Carcinogenesis: mutations and mutagens.

In normal human cells there is a steady accumulation of mutations with time. We argue that the great majority of these mutations arise spontaneously and are due to endogenous factors or processes that damage DNA. A small fraction of these mutations converts a normal cell into a cell that is initiated towards the development of cancer.

In vivo expression of interleukin-1 beta (IL-1 beta), IL-2, IL-4, IL-6, tumour necrosis factor-alpha and interferon-gamma in the fetal murine thymus.

Cytokines are known to play a role in T-cell lymphopoiesis as potent growth or differentiation factors, but many experiments focusing on their role in the thymus have been conducted only in vitro. We have thus used frozen sections obtained from fetal thymuses of normal C57BL 6 mice to investigate by immunohistochemistry the presence of interleukin-1 beta (I4-1 beta), IL-2. IL-4.

Prevention of murine radiogenic thymic lymphomas by tumor necrosis factor or by marrow grafting.

Background: Split-dose irradiation (1.75 Gy given weekly for 4 weeks) of C57BL/Ka mice induces the emergence of preleukemic cells (PLCs). These cells develop into leukemic cells after a latency period of 3-6 months.

Removal of sialic acid from the surface of human MCF-7 mammary cancer cells abolishes E-cadherin-dependent cell-cell adhesion in an aggregation assay.

MCF-7 human breast cancer cells express E-cadherin and show, at least in some circumstances, E-cadherin-dependent cell-cell adhesion (Bracke et al., 1993). The MCF-7/AZ variant spontaneously displays E-cadherin-dependent fast aggregation; in the MCF-7/6 variant, E-cadherin appeared not to be spontaneously functional in the conditions of the fast aggregation assay, but function could be induced by incubation of the suspended cells in the presence of insulinlike growth factor I (IGF-I) (Bracke et al.

Spontaneous and induced apoptosis after whole body radiation exposure: experimental approaches. Observations in radio-induced thymic lymphomagenesis.

Radio-induced thymic lymphomagenesis is associated with alterations in the balance between thymocyte subsets and cytokinetic perturbations. The objectives of this work were to investigate whether these alterations are associated with alterations in the basic levels of thymocyte apoptosis. For this purpose, we tested DNA fragmentation by gel electrophoresis, analyzed DNA content by propidium iodide staining of ethanol fixed cells and looked for DNA strand breaks on tissue sections by in situ end labeling.

High tumor necrosis factor alpha (TNF-alpha) production in Trypanosoma cruzi-infected pregnant mice and increased TNF-alpha gene transcription in their offspring.

Since tumor necrosis factor alpha (TNF-alpha) is known to be involved in the feto-maternal relationship, this cytokine was studied in Trypanosoma cruzi-infected pregnant BALB/c mice and their fetuses and offspring. Pregnant chronically infected mice displayed significantly higher levels of circulating TNF-alpha than animals either only infected or only pregnant. TNF-alpha was undetectable in sera of uninfected and nonpregnant mice as well as in breast milk obtained from infected and uninfected animals.

Analysis by in situ hybridization of cytokine mRNA expression in the murine developing thymus.

We have used in situ hybridization to investigate the expression of IL-1, IL-2, IL-4, IL-6 and IFN-gamma genes by thymic cells during fetal development in mice. Two waves of mRNAs were detected in thymic cells for IL-1 at days 16 and 19 of gestation, for IL-2 at days 14 and 18, and for IL-4 at days 14 and 16. Three peaks for IL-6 were observed at days 13, 17 and around birth.

Enlarged cell-associated proteoglycans abolish E-cadherin functionality in invasive tumor cells.

Mouse and dog epithelial cell lines, expressing high levels of the Ca(2+)-dependent cell-cell adhesion molecule E-cadherin in vitro, generated invasive and metastatic tumors in athymic mice. From these tumors, neoplastic cell lines were isolated. All ex vivo isolates retained high expression levels of E-cadherin at their surface.

Analysis by in situ hybridization of cells expressing mRNA for tumor-necrosis factor in the developing thymus of mice.

We have used in situ hybridization to investigate the expression of TNF-alpha genes by thymic cells during fetal development in mice. In 14-day-old fetal thymuses, very scarce cells produce TNF-alpha mRNA. A second phase of cytokine gene expression starts on day 16.

Drug distribution in dog brain studied by positron emission tomography.

We used positron emission tomography to monitor the distribution of radioactivity in dog brain and muscle following i.v. administration of 11C-labelled antipyrine, imipramine, and quinidine.

Cyclotron production of carrier-free 66Ga as a positron emitting label of albumin colloids for clinical use.

A method for producing carrier free 66Ga (T1/2:9.4 h; beta +) by 4He bombardment of natural copper targets is presented. 66Ga is formed by means of the 63Cu (4He, n) 66Ga reaction.

Clinical comparison of 11C-ACPC (aminocyclopentane carboxylic acid) and 13N-ammonia as tumour tracers.

Positron emission tomography is a potential method for exploring the biochemical behaviour of tumours. In 28 patients with known neoplastic lesions a comparison was made between two agents which are known to be accumulated in malignant tumours, viz. 13N-ammonia and 11C-aminocyclopentane carboxylic acid (ACPC).

PET studies of changes in cerebral blood flow and oxygen metabolism after unilateral microembolization of the brain in anesthetized dogs.

Cerebral blood flow and oxygen metabolism have been measured with the steady-state oxygen-15 technique and positron emission tomography in anesthetized dogs. Regional microembolization was induced by infusing Sephadex particles (diameter, 40 micron) into one of the common carotid arteries. In the first series of experiments, 2.

Kinetics of 13N-ammonia incorporation in human tumours.

After intravenous injection of 13N-labelled ammonia time-activity curves were obtained in a series of malignant neoplasms in man from serial cross-sectional scans through the tumour, using positron emission tomography. Low noise images with virtually no artefacts were obtained using a maximum likelihood reconstruction technique. Tracer concentration was expressed as a fraction of the injected dose ml-1 of tumour tissue.

Uptake of 13N-ammonia by human tumours as studied by positron emission tomography.

Tumour uptake of 13N-labelled ammonia was studied by means of positron emission computerised axial tomography in 46 patients with various extensive neoplastic conditions. Eleven of the patients have been followed sequentially before, during and after radio- and/or chemotherapeutic treatment. Substantial accumulation of 13NH3 (up to five times the amount found in comparable normal tissues) was noted in some cases of breast cancer and their metastases, as well as in soft tissue sarcomas, in malignant neck nodes secondary to head and neck tumours, in lung tumours and their metastases, in melanomas, in malignant lymphomas, in metastasis prostatic carcinoma and in the case of ovarian carcinoma examined.

Visualization of muscles involved in unilateral tremor using 13N-ammonia and positron emission tomography.

Using positron emission computerized tomography (PCT), a high uptake of IV injected 13N-ammonia was observed in the muscles of the right forearm and leg of a patient with a rightsided static tremor. In some muscles the concentration of 13NH3 was 8.5 times higher than in the symmetrical normal limb.

A correlation between the effects of calcium on intercellular adhesion and electrostatic repulsion between cells.

Calcium ions enchance the mutual adhesiveness of HeLa cells harvested from suspension cultures in which growth is density inhibited. No significant effect of calcium is observed on the mutual adhesiveness of HeLa cells from fast growing suspension cultures. Agglutinative titration of the cells using poly-L-lysine, mol.

Putrescine-promoted mutual adhesiveness of HeLa cells from density-inhibited suspension cultures.

The mutual adhesiveness of HeLa cells harvested from density-inhibited suspension cultures was significantly enhanced by the addition of putrescine. No significant effect was observed on the adhesiveness of HeLa cells harvested from fast-growing suspension cultures. The effect on density-inhibited cells was abolished by previous treatment of the cells with neuraminidase.

Thermal transitions in the adhesiveness of HeLa cells: effects of cell growth, trypsin treatment and calcium.

The intercellular adhesiveness of density-inhibited (D.I.) and fast-growing (F.

Cell size and mutual cell adhesion. II. Evidence for a relation between cell size, long-range electrostatic repulsion and intercellular adhesiveness during density-regulated growth in suspension.

The strength of the long-range electrostatic repulsion forces on HeLa cells is measured by agglutinative titration using low molecular weight polylysine (M.W. 11,000).

Cell size and mutual cell adhesion. I. Increase in mutual adhesivenes of HeLa cells from density-inhibited suspension cultures by hypotonic treatment.

HeLa cells harvested from density-inhibited or fast growing suspension cultures, were incubated in NaCl solutions of different tonicity. Cell size enlargement produced by hypotonicity is accompanied by an increased sedimentation rate of the density-inhibited cells, whereas no appreciable change is observed in the sedimentation rate of fast growing cells. Hypotonicity also has no effect on the sedimentation rate of density-inhibited cells which previously had been treated with neuraminidase or trypsin.