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T Rytömaa

Publications and source records attributed to T Rytömaa.

16 recordsLinked to original sources
PubMed1990

UV light and ionizing radiations cause programmed death of rat chloroleukaemia cells by inducing retropositions of a mobile DNA element (L1Rn).

The long interspersed repetitive DNA, L1 or LINE, is a class of mobile genetic elements which can amplify in the cell genome by retroposition, i.e. by a mechanism similar to that of retroviruses. We have shown before that in rat chloroleukaemia cells, maintained in suspension culture in vitro, this element is spontaneously transcriptionally activated at about half of the maximal population density. About 24 h later an explosive amplification of the L1 element is seen in DNA: about 300,000 copies are inserted into apparently random locations in the cell genome, thus creating an outburst of lethal mutations. Dead cells display morphological features typical to programmed death. The present results show that UV light and ionizing radiation induce rapid, premature activation of the L1Rn element during the fast exponential growth of chloroleukaemia cells, and that also this exogenously induced activation is followed by programmed cell death. Transcriptional activation of the L1Rn element can be very strong after the UV exposure: at least 70-fold. Severe hyperthermia, lethal to the cells, does not lead to L1Rn activation (actually a marked suppression is seen) and the mode of phenomic death is necrosis. Some biological implications of the results are discussed.

Animals↗
PubMed1989

The accident at Chernobyl and outcome of pregnancy in Finland.

OBJECTIVE: To evaluate the outcome of pregnancy in Finnish women after the accident at the Chernobyl nuclear power plant on 26 April 1986. DESIGN: Geographic and temporal cohort study. SETTING: Finland divided into three zones according to amount of radioactive fallout. SUBJECTS: All children who were exposed to radiation during their fetal development. Children born before any effects of the accident could be postulated--that is, between 1 January 1984 and 30 June 1986--served as controls. INTERVENTIONS: Children were divided into three temporal groups: controls, children who were expected to be born in August to December 1986, and children who were expected to be born in February to December 1987. They were also divided, separately, into three groups according to the three geographic zones. END POINT: Incidence of congenital malformations, preterm births, and perinatal deaths. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in the incidence of malformations or perinatal deaths among the three temporal and three geographic groups. A significant increase in preterm births occurred among children who were exposed to radiation during the first trimester whose mothers lived in zones 2 and 3, where the external dose rate and estimated surface activity of caesium-137 were highest. CONCLUSIONS: The results suggest that the amount of radioactive fallout that Finnish people were exposed to after the accident at Chernobyl was not high enough to cause fetal damage in children born at term. The higher incidence of premature births among malformed children in the most heavily polluted areas, however, remains unexplained.

Abnormalities, Radiation-Induced↗
PubMed1988

Suicidal death of rat chloroleukaemia cells by activation of the long interspersed repetitive DNA element (L1Rn).

Rat chloroleukaemia cells, maintained in suspension culture in different media, show rapid exponential growth without cell loss. At about half of the maximal population density the long interspersed repetitive DNA element (L1Rn) is suddenly transcriptionally activated without any obvious exogenous reason. Population growth is then inhibited and, within about 24 h after reaching the maximal density, the population undergoes programmed death (apoptosis). Suicidal cell death is caused by sudden incorporation, apparently by retroposition via an RNA intermediate, of about 300,000 copies of the L1Rn element into random locations in the cell genome, thus creating lethal mutations. The preceding growth inhibition is associated with repression, to an undetectable level, of c-Ki-ras expression. Up to the point of massive L1Rn incorporation and cell death, all phenomena are quickly reversible by subculturing; medium change alone is not sufficient. Biological implications of these surprising findings are discussed.

Animals↗
PubMed1987

Cell kinetic analysis of a murine macrophage cell line.

For the present study, which was performed to find a reliable method suitable for determination of the cell kinetic parameters of a continuous cell line, use was made of the macrophage cell line J774.1. The doubling time of the cell population was approximately 27 h. The continuous labeling curve showed that all the cells divide and almost no quiescent cells occur. The cell-cycle time as determined from the curve of the labeled cells in mitosis, the course of the stathmokinetic index, and time-lapse videorecordings, was about 19 h. The discrepancy between the population doubling time and the cell-cycle time must be due to death and disintegration of cells during culture in vitro. The results indicate that the doubling time of a cell population is not a reliable parameter to determine the kinetics of a population of continuously proliferating cells and that determination of the course of the stathmokinetic index offers a rapid and simple method to establish the cell-cycle time reliably.

Animals↗
PubMed1979

Chalones: concepts and results.

Control of cell proliferation is executed, in part, by means of negative feedback, utilizing cell-line specific messenger substances called chalones. Although knowledge of chalone chemistry is still in its infancy, the reality of the concept can no longer be reasonably questioned. In particular, it has recently been shown that chalones are even capable of causing tumour regression both in animals and in man. In addition to overviewing the chalone concept, we show here that the chalone-induced tumour regression is readily explained in simple and plausible terms.

Animals↗
PubMed1979

Granulocytic chalone inhibits rapidly proliferating committed murine progenitor cells (CFU-C).

Bovine leucocyte extract containing the granulocytic chalone inhibited proliferation of rapidly, but not slowly, prliferating murine CFU-C. The precursors of CFU-C, i.e. multipotent colon-forming stem cells (CFU-S), were apparently not affected. Inhibition of proliferation was detected as a decreased killing of DNA synthesizing cells in diffusion chamber cultures by hydroxyurea, after pre-treatment with the extract.

Animals↗
PubMed1979

Granulocytic chalone is not a polyamine complex.

Recent studies have indicated that tissue extracts may contain sufficient amounts of free polyamines to account for the inhibitory effect of the extracts and hence mask any authentic chalone action. It has also been reported that bound polyamine may be the active moiety of some chalones. We show here that in our granulocytic and lymphocytic chalones polyamines, either free or bound, are not responsible for the inhibitory effects of the preparation.

Animals↗
PubMed1977

Regulation of maturation rate of mouse granulocytes.

Regenerating mouse bone marrow cells were cultured i.p. in diffusion chambers (DC) to study factors affecting the maturation rate of granulocyte precursors. One day after exposing 3-day-old DC cultures to 3H-thymidine the cultures were harvested, and labelled proliferative and non-proliferative granulocytes were counted in radioautographs. The relative maturation rate--defined as the fraction of proliferative precursors maturing into the non-proliferative compartment per unit time--could be increased by different experimental procedures that inhibit cell production. Inhibition was obtained (a) by increasing culture cellularity; (b) by implanting DC into normal rats or rats with huge s.c. chloroma tumours rather than into mice; and (c) by treating the cells with leucocyte extracts (granulocyte chalone) during the last day of culture. Furthermore, a sudden inhibition of rapidly proliferating granulocytes by leucocyte extracts resulted in an increase (apparently transient) in the absolute number of labelled non-proliferative granulocytes. Such an increae was not detected in experiments involving a stronger or sustained inhibition of granulopoiesis, evidently because the size of the precursor population had been markedly reduced.

Animals↗
PubMed1976

Effect of the Hewitt keratinizing epidermal carcinoma on cell proliferation in different organs of the host mouse and in human psoriatic skin cultured in diffusion chambers.

Incorporation of 3H-thymidine into different squamous epithelia and other tissues was studied in mice bearing the Hewitt keratinizing epidermal carcinoma with a raised epidermal chalone content in the body. The results showed that DNA synthesis in the tumour-bearing mice was inhibited strongly in the epithelium of the ear (c.80%), moderately in the epithelium of the back skin and the foot (c.55%), and weakly in the epithelium of the tongue and the cornea (c.25%). These inhibitions appear to be specific in nature, because cell proliferation was not detectably affected in the sebaceous gland, intestinal epithelium, bone marrow, and thymus lymphocytes. Thymus size, however, was reduced in the tumour-bearing mice compared with controls, and 3H-thymidine uptake was depressed in the spleen and to some extent also in the lymph nodes, possibly owing to non-specific stress. Labelling index of human psoriatic epidermis was suppressed in diffusion-chamber cultures carried by the tumour-bearing host mice compared with controls. However, this reaction was probably not specific in nature, because the labelling index of mouse bone-marrow cells was also decreased when grown in tumour-bearing animals.

Animals↗
PubMed1976

Effect of granulocyte chalone on acute and chronic granulocytic leukaemia in man. Report of seven cases.

This study reports results from the first clinical tests in which 7 patients with myeloid leukaemia (5 acute and 2 chronic leukaemias in metamorphosis) were treated from 4 to 45 days with granulocyte chalone, the tissue-specific endogenous inhibitor of granulopoiesis. It was observed that i.v. injection of partially purified chalone inhibits proliferation of leukaemic, and presumably also normal granulocytic cells, leaving all other cell types unaffected. Inhibition of leukaemic growth was distinct in 6 of the 7 patients; in 5 cases the inhibition was followed by acutal regression of the leukaemia, lasting up to several months in the absence of any maintenance therapy, and in one case the treatment led to a complete remission. Chalone treatment also resulted in an enhancement of erythropoiesis and megakaryopoiesis, and in phenomena some of which were totally unexpected, such as immunostimulation and a remarkable resistance to bacterial infections in the presence of extreme granulocytopenia. This study shows that granulocyte chalone is biologically active against myeloid leukaemia in man, but not that the therapeutic value of the impure chalone is superior to modern cytostatic drugs. Long-term therapeutic trials were not possible with the partially purified preparations available, mainly because of side-effects which prevented adequate dosing.

Adult↗
PubMed1975

Biology of the granulocyte chalone.

Granulocyte chalone is a cell line-specific, species non-specific regulator substance, which inhibits cell proliferation in the granulocyte system in a reversible manner. The existence and specificity of action of this substance has been shown both in vitro and in vivo in widely different assay conditions and using a broad spectrum of assay techniques. Granulocyte chalone inhibits cell proliferation in the transit populations of the granulocyte system; it seems to act at the level of cell membrane and divert cells from the G1 phase to the "G0" phase with some direct or indirect effect on S phase cells as well. The substance is non-cytotoxic and it has no detectable effect on any other tissue than normal and leukaemic granulocytes even after long-lasting in vivo treatment. Granulocyte chalone offers an exciting potential for the treatment of myeloid leukaemia and, therefore, the substance is of more than academic interest.

Cell Membrane↗