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Biomedical subjects

R Sennerstam

Publications and source records attributed to R Sennerstam.

12 recordsLinked to original sources

Partition of protein and DNA during cytokinesis in human breast cancer cell lines.

Three human breast cancer cell lines (HTB-126, MDA-231, and HTB-122) with DNA index (DI) values between 1.26 and 1.72 were analysed together with a diploid mouse embryonal carcinoma cell line (PCC3) by a TV-video time-lapse technique (pedigree analysis). Cytochemical parameters (DNA and proteins) were studied in individual cells in a rapid scanning microspectrophotometer. Post-mitotic sister cell pairs were analysed after Feulgen-naphthol-yellow staining. The DI values of the cell lines were selected to reflect various well-known clinical ploidy entities differing in malignancy potentials. A mitotic disturbance of the partition of DNA and protein to daughter cells was found in particular in MDA-231 closest to the triploid DNA modal value (DI = 1.37). Duration of mitosis was considerably longer in the near triploid line compared to the other lines. The MDA-231 line was also least sensitive to suboptimal growth conditions. This report calls attention to a possible causality between mitotic error and intraclonal genotype and cell mass heterogeneity.

Aneuploidy

DNA and nuclear protein characteristics in non-neoplastic and neoplastic endometrial tissue.

Feulgen-DNA and nuclear protein (NP) measurements were performed on non-neoplastic and neoplastic endometrium. Non-neoplastic endometrial cells were exclusively characterized by euploid nuclear DNA content. The NP content may vary significantly in relation to the proliferative stage as reflected by a 2-3-fold increase NP/DNA ratio in growing as compared to growth arrested cells. Endometrial adenocarcinomas could be subdivided into euploid and aneuploid types. The euploid tumors were found to exhibit DNA and NP characteristics comparable with those of normal tissue. In contrast, aneuploid tumors showed DNA and NP characteristics indicating increased proliferative activity as well as a pronounced disorder between the DNA and protein cycle.

Biomarkers, Tumor

Dissociation of cellular protein and DNA content in mild and moderate dysplasia as a reflection of the degree of aneuploidy in cancer.

Tumor progression was analyzed in vivo. The bronchial epithelium in five beagle dogs was weekly treated by 20-methylcholanthrene (20-MC). Bronchial cells were harvested before each application of the drug. The cytologic criteria used in the diagnostic procedure were based on a grading developed for Papanicolaou-stained preparations of human squamous bronchial epithelium. The cells were then destained and restained by Feulgen-naphthol yellow S technique. An increased variation in the protein/DNA ratio was an early event in tumorigenesis; it occurred even before aneuploid cells appeared in mild dysplasia, as compared with the control cells. A large increase in the coefficient of variation (CV) in the protein/DNA ratio in mild dysplasia vis-a-vis the control cells was positively correlated to the degree of aneuploidy occurring later in tumorigenesis. These results were compared with the findings in breast cancer cells from patients with near-diploid, aneuploid and near-tetraploid tumors. The CV in the protein/DNA ratio was significantly higher in the aneuploid tumors, indicating an increased dissociation between cell growth and DNA synthesis.

Aneuploidy

Evidence for an intraclonal random shift between two types of cell cycle times in an embryonal carcinoma cell line.

In a recent paper we reported the discovery of an intraclonal bimodal-like cell cycle time variation within the multipotent embryonal carcinoma (EC) PCC3 N/1 line growing in the exponential phase in the undifferentiated state. The variability was found to be localized in the G1 period. Furthermore, an inverse relation between cell size and cell generation time was found in the cell system analysed. It was suggested that the bimodal-like intraclonal time variability previously reported was attributable to an intraclonal shift between two types of cell-growth-rate cycles and that the cell-growth cycle has a supramitotic character, being dissociated from the DNA-division cycle. The growth rate heterogeneity in the cell population was found to need three cell cycles to reach full dispersion in time. This was assumed to be due to a decreased inheritance from sister cell pairs to second cousin cell pairs. Thus, the interesting feature is that in one and the same multipotent cell line there was evidence for an intraclonal instability with a random shift between two types of cell cycle differing in the duration of their G1 period.

Cell Line

Partition of protein (mass) to sister cell pairs at mitosis: a re-evaluation.

Since the 1960s it has been thought that there is to some extent a difference in the partition of mass to daughter cells at mitosis. Recent studies using modern techniques give further support to such a phenomenon, which has become almost an axiom in cell biology. It has been suggested that such unequal distribution of metabolic constituents at mitosis contributes to the dispersion in cell generation times. In the present work, PCC3 embryonal carcinoma (EC) cells were studied as undifferentiated G1 sister pairs by microspectrophotometry (MSP) following Feulgen-Naphthol Yellow staining (FNYS), in order to evaluate their protein content. Despite the considerable intraclonal intermitotic time heterogeneity found in undifferentiated PCC3 EC cells, it was concluded thta the postmitotic difference in mass (protein) between sister cell pairs exerts a minimal influence upon the cell population mass variability, whereas it was deduced to have an influence upon variation in interphase time duration when comparing sister cell pairs. This offers a cell-physiological explanation to the randomly distributed difference repeatedly found between sister cell generation times. Furthermore, there was no correlation seen between the mass difference found between sister cell pairs postmitotically and the size of the mother cell.

Animals

Growth rate regulation and random transition. A study performed on embryonal carcinoma cell lines. I.

Analyses of cell-cycle characteristics of the three embryonal carcinoma (EC) cell lines F9, PCC3 N/1 and PCC4 Azal, have been performed. The three lines reflect successive stages in early mouse embryogenesis as regards cell surface antigens and cell-cycle characteristics. In an attempt to understand changes in cell-cycle characteristics occurring during early embryogenesis, the two-random transition probability (TP) model was applied to the EC-cell system--and particularly to the F9 line. By utilizing an intraclonal heterogeneity in intermitotic times found in these EC lines, a growth-regulating point was introduced as a modification of the two-random TP model. The modified model was found to be very useful when demonstrating the cell-cycle growth kinetics of the F9 line. The model is used in an accompanying paper to extend the analysis of cell-cycle characteristics in undifferentiated EC cells.

Animals

Cell growth and cell division: dissociated and random initiated? A study performed on embryonal carcinoma cell lines. II.

The 'random transition probability' cell-cycle models have so far failed to convincingly link the transition events with phenomena describable by biochemical methods. The study presented was carried out on the F9 and PCC3 N/1 embryonal carcinoma (EC) cell lines. We now report an extended analysis of the two-random transition probability (TP) model and preliminary results are presented showing that the deterministic L period in that model can be regarded as reflecting the 'cell-growth cycle'. Evidence is presented that suggests that the 'cell-growth cycle' is a supramitotic deterministic phase--i.e. starting in one cell cycle and being completed in the next following G1 period and dissociated from the 'DNA-division cycle'. This phenomenon makes an interesting contribution to the old knowledge of a stepwise G1 prolongation during early embryogenesis in yielding a mechanism by which the cell can alter the ratio of nucleus to cytoplasm prior to the onset of gene expression.

Animals

A comparative study of the cell cycles of nullipotent and multipotent embryonal carcinoma cell lines during exponential growth.

Three embryonal carcinoma (EC) cell lines F9, PCC4 Azal, and PCC3 N/1 with a common origin from the transplantable ascites teratoma OTT6050 were analyzed with regard to cell cycle characteristics during exponential growth in the undifferentiated state. The three lines, in the sequence mentioned, have been shown to represent successive stages in early normal mouse embryogenesis from morula to blastocyst, as reflected in their cell surface antigens. In the multipotent lines an increased intraclonal variability in intermitotic times was found when analyzing family trees. In the PCC3 N/1 line the distribution was almost bimodal. The increased intermitotic time variability was found to be represented in the G1 period that varied from less than 1 hr up to about 6 hr in the PCC3 N/1 line, with a mean value of 3.4 hr. The G1 period of the F9 line had a range of only 3.5 hr, with a mean value of 1.5 hr. The S-G2 period was found to be very similar in length in all three lines.

Alkaline Phosphatase

Is there a changing epidemiology of premalignant lesions of the cervix? Results of cytologic screening of pregnant women.

The selection of women approached for cytologic screening is based on previous studies on age distribution and prevalence and consequent considerations on the risk of developing invasive carcinoma. In order to check if this is appropriate the results of the screening of pregnant women being selected irrespective of their age has been studied for two periods, 1961-64 and 1972. The frequency of lesions was remarkably high among the teenagers of both periods. A significant increase in the incidence of lesions was noted for the period 1972. This increase is most evident in the ages 21 to 30. A shift to more severe lesions was found among the teenagers and in the groups between 31 and 40. In conclusion more effort should be made with respect to cytologic screening of young women, particularly when pregnant. The increased frequency of cytologic atypias among women between 21 and 30 should focus the attention to the possibility that the epidemiology or premalignant lesions of the uterine cervix is changing.

Adolescent