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DNA ploidy pattern in human chronic liver diseases and hepatic nodular lesions. Flow cytometric analysis on echo-guided needle liver biopsy.

BACKGROUND: Significantly elevated fractions of diploid hepatocytes and reduction in the polyploid populations have been reported in human and experimentally induced hepatocellular carcinomas (HCC). This study was conducted to determine how these changes are related to conditions that often precede HCC, such as chronic hepatitis, cirrhosis, and premalignant focal nodules in cirrhotic livers. METHODS: Ultrasound-guided needle biopsy specimens of the liver were obtained from patients with chronic hepatitis, cirrhosis, or ultrasonographically diagnosed nodules within cirrhotic livers; biopsy specimens also were taken from patients without hepatic disease. DNA flow cytometry was performed on isolated nuclei to determine the percentages of diploid, tetraploid, and octaploid hepatocytes; the S-phase fraction for each diploid peak and the diploid/polyploid (tetraploid + octaploid) ratio also were calculated. Part of each specimen was reserved for evaluation of hepatocyte binuclearity. RESULTS: Chronically hepatitic (18 patients) and cirrhotic (18 patients) livers showed significantly increased diploid/polyploid ratios, with respect to normal livers, that were significantly correlated with decreases in hepatocyte binuclearity. This trend was even more marked in euploid nodules (4 premalignant and 5 malignant), in which the S-phase fractions were significantly higher than those of normal liver; aneuploidy was found in 6 of 11 malignant and 2 of 6 premalignant nodules.

Aged↗

Diagnostic and prognostic value of DNA ploidy and cell nuclearity in ultrasound-guided liver biopsies.

BACKGROUND: Focal nodule lesions in patients with cirrhotic livers may be visualized by using imaging techniques; however, the diagnostic and prognostic judgment of biopsies from borderline lesions may be difficult using conventional histologic criteria. METHODS: The diagnostic and prognostic value of DNA ploidy analysis determined by image cytometry of Feulgen-stained isolated hepatocytes was investigated in ultrasound-guided biopsies from 50 nodular lesions found in patients with cirrhotic livers (39 hepatocellular carcinomas [HCCs] and 11 macroregenerative nodules) and from 10 patients with livers affected by viral chronic hepatitis. Of the 11 macroregenerative nodules, 7 presented a subsequent neoplastic behavior. Specimens from the morphologically normal livers of five patients who underwent liver surgery served as control tissues. Image cytometry was performed on Feulgen-stained cytologic preparations, obtained by enzymatic digestion of formalin fixed biopsies. The DNA ploidy of the main stem line and the distribution of mononucleated and binucleated hepatocytes (nuclearity) were compared using histologic diagnosis, Edmondson's grade, tumor size, and patient follow-up. RESULTS: The main stem line was peridiploid in all benign specimens and in 31 clinically confirmed HCCs, peritetraploid in 11 HCCs, perioctaploid in 1 HCC, and aneuploid in 3 HCCs. The fraction of mononucleated polyploid hepatocytes was found to be the best diagnostic parameter in euploid HCCs and was significantly correlated with the Edmondson grade and the nodular size. Survival information was available for 43 patients, with a median observation period of 350 days. A DNA ploidy value of the main stem line greater than 3c was an important determinant of survival as a single parameter and in association with histologic grade and greatest dimension of tumor. CONCLUSIONS: This study suggests that the ploidy distribution analysis of mononucleated and binucleated hepatocytes can provide valuable information for making correct diagnoses and for predicting survival outcome for patients with HCCs.

Biopsy↗

Mucinous borderline and malignant tumors of the ovary. A clinicopathologic and DNA ploidy study of 92 cases.

BACKGROUND: The morphologic spectrum of ovarian mucinous tumors is well known, but the features that predict aggressive behavior are still controversial. METHODS: Ninety-two cases of primary ovarian mucinous tumors with atypical epithelial proliferation and/or stromal invasion were analyzed histologically and by DNA flow cytometry, and the results were correlated with clinical findings. RESULTS: The authors reviewed 57 intestinal mucinous borderline tumors (IMBT), 3 endocervical-like mucinous borderline tumors (EMBT), 21 noninvasive mucinous carcinomas (NIMC), and 11 invasive mucinous carcinomas (IMC). The 5-year survival rate for Stage I tumors was: IMBT 100%, EMBT 100%, NIMC 94% and IMC 60%. The 5-year survival of Stage II-IV tumors was: IMBT 50%, NIMC 33% and IMC 0%. Forty-four IMBTs were diploid, and 4 were aneuploid. All six high stage IMBTs were diploid. Two EMBTs were diploid, and one was aneuploid. There were seven diploid, four polyploid, and six aneuploid NIMCs. Two of the three lethal NIMCs were aneuploid. Four IMCs were diploid, and four were aneuploid. Of these, only the diploid Stage I IMCs were nonlethal. All NIMCs that recurred or presented with metastases had been sampled inadequately. High stage tumors with pseudomyxoma peritonei (PP)-type lesions often were associated with pseudomyxoma ovarii of the cellular type. CONCLUSIONS: Mucinous tumors with stromal invasion or presenting with PP had a definite malignant behavior. All other atypical mucinous tumors, when confined to the ovary and optimally sampled, had an excellent prognosis. DNA ploidy analysis may prove useful in determining the risk of progression, especially in Stage I IMCs.

Adenocarcinoma, Mucinous↗

Multiple copies of mutant BRCA1 and BRCA2 alleles in breast tumors from germ-line mutation carriers.

Inactivation of the BRCA1 and BRCA2 breast cancer susceptibility genes has been reported to occur via a germ-line mutation of one allele and a somatic loss of the remaining wild-type allele. We investigated the genetic mechanisms behind the second event in breast tumors from 17 BRCA1 and eight BRCA2 germ-line mutation carriers, as compared with 21 sporadic breast tumors. Microsatellite markers intragenic or in close proximity to both genes were used to analyze imbalances between the mutant and wild-type alleles. The actual and relative gene copy numbers were scored by fluorescence in situ hybridization (FISH) analysis of tumor cells using locus and centromere specific probes. All but one of the informative BRCA1 and BRCA2 tumors exhibited allelic imbalance and loss of the corresponding wild type allele. In contrast to sporadic tumors, however, where allelic imbalance at the BRCA1 and BRCA2 loci correlated well with relative copy number losses by FISH, a simple reduction to a single copy (average copy number ratio 2:1) was found in only two BRCA1 (12%) and four BRCA2 (50%) tumors. The majority of BRCA1 and BRCA2 tumors showed a copy number reduction (relative to reference probe with ratios 4:2, 3:2, 4:3) at corresponding loci, suggesting that a specific physical deletion of the wild-type BRCA gene allele has been followed by a duplication of the remaining mutant allele via polyploidization. Several tumors contained multiple copies of BRCA1 and BRCA2 genes without relative copy number changes, implying that loss of wild-type alleles is executed by alternative mechanisms such as mitotic recombination, non-disjunctional chromosomal loss with or without reduplication, or by gene conversion. A paradoxical relative copy number gain of the mutant allele was evident in three BRCA1 tumors (18%), which could be of biological relevance if a dominant negative or gain-of-function model was ascribed for certain BRCA1 mutants. Our results indicate that complex genetic alterations are operational at the BRCA1 and BRCA2 loci in tumors from genetically predisposed individuals.

Alleles↗

Ultrastructure of decidualization in the pseudopregnant rat.

The ultrastructure of the endometrial stroma in rats bearing deciduomata was examined in detail on day 9 (day of vaginal cornification = day 0) of pseudopregnancy, together with the development of deciduomata from day 4 to day 8. Five major regions were recognizable on day 9. 1) In the basal zone, which contributes to endometrial regeneration following decidualization, stromal cells remained fibrocyte-like and were separated by wide bands of collagen fibrils. Capillaries were fenestrated and large. 2) The capsule surrounding the antimesometrial (region of the) deciduoma was composed of flattened cells, showing mitosis, which appeared to provide a source of appositional growth of the deciduoma. 3) The large, tightly packed, polyploid cells of the antimesometrial deciduoma showed morphological evidence of protein synthesis activity, an absence of smooth endoplasmic reticulum, and surface specializations suggestive of adhesion (adherens junctions), communication (gap junctions), and maintenance of an extensive surface area (lamellar processes). These cells came into very close apposition with capillary endothelial cells, which were seldom fenestrated, lacked any continuous basal lamina, and showed evidence of high metabolic activity. 4) The loosely packed mesometrial deciduoma contained a structurally supportive, "fixed" population of spiny cells and a "free" population of granulated cells and their putative precursors, together with a meshwork of large, sinusoidal capillaries whose endothelium was generally supported by a basal lamina. 5) The peripheral parts of the glycogenic area, which was structurally similar to the mesometrial deciduoma, contained many grossly enlarged intercellular spaces of undetermined function. The stromal cells at day 4, which give rise to all non-vascular elements except the granulated cells mentioned above, were structurally simple and fibrocyte-like. Only two distinct regions, subepithelial and deep, were recognizable. Capillaries at day 4 generally possessed a continuous endothelium, with a complete basal lamina and many pericytes. Between days 5 and 8, the stromal cells showed divergent forms of differentiation according to their position in the endometrium. Ultrastructural differentiation of the vasculature also showed divergence according to position, leading to the various types of capillaries seen at day 9. Regional variation, and high levels of structural organization, characterize the "programmed" decidual response in the pseudopregnant rat.

Animals↗

Regulation of anterior cell-specific mec-3 expression during asymmetric cell division in C. elegans.

The homeobox-containing mec-3 gene of C. elegans is expressed in 10 mechanosensory neurons and is necessary for these cells to acquire their fate. All the mec-3-expressing cells are anterior daughters from an asymmetric cell division. In this paper, we examine the expression of a mec-3--lacZ fusion in the presence of mutations that may disrupt asymmetric cell division or anterior-posterior positional information, as well as mutations that may specifically alter mec-3 expression. A mutation in lin-17 causes production of additional mec-3-expressing cells and can have its effect on the cell division that produces a mec-3-expressing cell. In a lin-5 mutant, in which postembryonic blast cells do not complete cell division and become polyploid, blast cells that would give rise to mec-3-expressing daughters instead express mec-3 themselves. In a lin-12 glp-1 double mutant, which is disrupted for many cell interactions in which two cells compete for the same fate, mec-3 expression is unaffected. These results are consistent with a model for asymmetric cell division in which the mec-3-expressing cell and its sister are different immediately upon cell division, rather than acquiring differences through later interaction with each other or their surroundings. lin-17 mutant animals also show defects in the position of the PVM cell and the PLM axons. Animals mutant in unc-73 and unc-40, known to have axon outgrowth defects, also show errors in PVM position and a low frequency of additional mec-3-expressing cells, as well as occasional secondary vulval protrusions, a common phenotype of lin-17 animals. Many other mutations have either no effect on mec-3 expression or an effect that can be largely predicted from previously known phenotypes: these include mab-5, mig-1, unc-53, egl-5, lin-32, and egl-27. unc-11 shows an unexpected and specific defect in mec-3 expression in the PVD neurons, but not in the other mec-3-expressing cells. Two mutations that suppress the egg-laying defect of unc-86 have no effect on the mec-3 expression defect in an unc-86 mutant.

Animals↗

Distribution of diploidy, polyploidy, and endoreduplication in fra(X) positive and negative lymphocytes, amniocytes, and chorionic villi.

Expression of fragile X [fra(X)] (q27.3) and endoreduplicated metaphases have been reported in methotrexate-treated (MTX) fra(X) cultures (Kerem B, Biotein R, Schaap T [1988]: Chromosoma 97: 6-10). Further, new data (Kimchi-Sarfaty C, Goitein R, Kerem B, Werner M, Medan B, Schaap T [1991]: Am J Med Genet, this issue) indicate that MTX may specifically induce polyploidy and endoreduplication in cells with the fra(X) mutation. To confirm and extend these results, we have studied short-term lymphocyte cultures incubated in M199, a folate deficient system, and RPMI-1640 in the presence and absence of 5-fluorodeoxyuridine (FUdR) exposure during the last day of a 4 day culture. No endoreduplicated cells were seen under these conditions and there was no change in the level of polyploidy. We also studied the distribution of polyploid and endoreduplicated cells in amniotic fluid and chorionic villus sample cultures from one fra(X) positive and 4 at-risk specimens. No increase in the incidence of polyploidy or endoreduplication was observed in cultures exposed to MTX for both 24 and 48 hours from a fra(X) positive amniotic fluid case. Cytogenetic results were fra(X) negative for the remaining 4 cases tested. There was significant discordance between our findings and those expected based on MTX-induced increased frequencies of polyploidy and endoreduplication. Thus, our studies do not confirm the reported correlation between the presence of FRAXA and increased frequencies of polyploidy and endoreduplication in MTX-exposed amniocyte cultures and there was no evidence for increased levels of polyploidy and endoreduplication in short-term fra(X) lymphocyte cultures exposed to non-MTX fra(X) induction.

Amniotic Fluid↗

Compensatory responses in the development of the brachial lateral motor column in triploid Rana pipiens.

Responses of the lateral motor column (LMC) in the frog spinal cord to various experimental manipulations generally are manifested in an adjustment of the number and sizes of the motor neurons. Analysis of the brachial LMC in induced-triploid Rana pipiens larvae as compared to diploid controls revealed a significant increase in nuclear size with a concomitant reduction in cell counts at all stages of development examined. These compensatory responses of the LMC to polyploidy in normal size frog larvae are consistent with results reported for other amphibian polyploid tissues and serve as a basis for exploring mechanisms of plasticity in the developing central nervous system.

Age Factors↗

Fermentation performance of engineered and evolved xylose-fermenting Saccharomyces cerevisiae strains.

Lignocellulose hydrolysate is an abundant substrate for bioethanol production. The ideal microorganism for such a fermentation process should combine rapid and efficient conversion of the available carbon sources to ethanol with high tolerance to ethanol and to inhibitory components in the hydrolysate. A particular biological problem are the pentoses, which are not naturally metabolized by the main industrial ethanol producer Saccharomyces cerevisiae. Several recombinant, mutated, and evolved xylose fermenting S. cerevisiae strains have been developed recently. We compare here the fermentation performance and robustness of eight recombinant strains and two evolved populations on glucose/xylose mixtures in defined and lignocellulose hydrolysate-containing medium. Generally, the polyploid industrial strains depleted xylose faster and were more resistant to the hydrolysate than the laboratory strains. The industrial strains accumulated, however, up to 30% more xylitol and therefore produced less ethanol than the haploid strains. The three most attractive strains were the mutated and selected, extremely rapid xylose consumer TMB3400, the evolved C5 strain with the highest achieved ethanol titer, and the engineered industrial F12 strain with by far the highest robustness to the lignocellulosic hydrolysate.

Cellulose↗

DNA ploidy pattern and tumour spread in gastric cancer.

The DNA ploidy pattern of gastric cancer was studied in 58 patients to investigate the heterogeneity between primary tumour and metastases. In both primary tumours and lymph node metastases, diploid patterns accounted for 33 per cent, whereas all liver metastases were aneuploid. The percentage of polyploid cells was higher in the liver metastases than in primary tumours and lymph node metastases. When the heterogeneity of DNA ploidy pattern between primary tumour and metastasis was evaluated, diploid tumours had a significantly lower rate of lymph node metastasis heterogeneity than aneuploid tumours. When the DNA ploidy pattern and survival were evaluated, the patients who had a diploid pattern in both primary tumour and metastasis had a significantly higher survival rate than the patients who had an aneuploid pattern in the primary tumour and metastasis (57 per cent versus 26 per cent at 5 years). These data suggest that cell heterogeneity is a common phenomenon in gastric cancer, and this may be important in the evolution of the disease. Furthermore, the role of the DNA ploidy pattern as a prognostic factor is emphasized.

DNA, Neoplasm↗

The DNA content of Purkinje cells in mammals.

Nerve cells have generally been assumed to have a diploid DNA content, typical of non-dividing somatic cells. However several reports have suggested that certain nerve cells types, notably Purkinje cells of the cerebellum, are polyploid. Other studies have contradicted these findings, stating Purkinje cells to be diploid. In this paper we reinvestigate the DNA status of Purkinje cells, in a variety of mammalian species. Cell DNA content is measured on tissue smears by Feulgen microspectrophotometry. Results show that for all species examined by us, Purkinje cells have, without exception, a DNA content comparable to that of somatic cells. A critical appraisal of the techniques used in those studies claiming a tetraploid DNA content for Purkinje cells leads us to believe our findings to be correct.

Animals↗

Effect of tetraploidy on dendritic branching in neurons and glial cells of the frog, Xenopus laevis.

Morphological aspects of four different groups of Golgi impregnated brain cells from a tetraploid strain of Xenopus laevis frogs were compared to analogous cells in comparably sized diploid frogs. The cells examined included neurons from the telencephalon, caudal hypothalamus, and optic tectum, and radial glial cells from the optic tectum. The brains of tetraploid frogs appeared grossly normal and were the same size and contained similar cell types as diploid brains. As observed in previous studies on polyploid amphibia, somal diameters increased significantly in tetraploid cells for each of the four groups of cells examined. Also, the total length of the dendritic arbors in tetraploid brain cells increased significantly by factors ranging from 1.4 to 2.4 times the total length of the analogous processes in diploid cells. Tetraploid neurons in the telencephalon and hypothalamus increased their arbor lengths predominantly by increasing the number of dendritic branches, while maintaining the average distance between branch points in the dendritic segments. In contrast, the tetraploid large pear-shaped neurons in the optic tectum had significantly longer terminal dendritic segments than the analogous diploid neurons, although these tetraploid neurons maintained their average number of dendritic segments per cell. Tetraploid tectal radial glial cells appeared to increase both their number of branches and the lengths of their terminal segments. Thus, the mode by which tetraploid brain cells achieved longer dendritic arbors varied from cell type to cell type. These results suggest a hypothetical basis for possible effects of genomic size on vertebrate brain structure and evolution at the cellular level.

Animals↗

Flow cytometry reveals a high degree of genomic size variation and mixoploidy in various strains of the acellular slime mold Physarum polycephalum.

High-resolution flow cytometry, using avian erythrocytes as an internal standard, was employed to study constitutive genome size variation of G2-phase nuclei of Physarum polycephalum strains during the macroplasmodial stage of their life cycle. Our results document a previously unknown extent of genome size variation and mixoploidy in this organism. The unimodal diploid strain Tu 291 displayed the largest genome of the strains tested; in contrast, the Colonia strain displayed only half of the Tu 291 G2-phase fluorescence, confirming its haploid nature. An additional strain, derived from a recent cross between Lu897 and Lu898 amoebae, must have arisen by selfing (propagation of only one of the parental genomes to the macroplasmodial stage), since its nuclei display close to the haploid G2-phase DNA content. The observation of a small fraction of corresponding diploid nuclei within the haploid population of this strain, while maintained as microplasmodia, supports the notion that meiosis in haploid strains may require the presence of diploid nuclei. Two of the descendants of the prototype haploid Colonia strain, which were kept for extended periods of time in submerse culture, proved to be near diploid and mixoploid. Polyploidization and subsequent loss of DNA thus seems to contribute to the extremes of genome size variation in Physarum. In addition to unimodal fluorescence distributions, a number of diploid strains displayed bi- and even trimodal distributions within harvests of a single G2-phase macroplasmodium. Analysis of these mixoploid strains by means of gaussian curve-fitting suggests that the smaller genome size differences in Physarum may arise in step-wise diminution of DNA in approximate units of 3-5% of the original Tu 291 genome.

DNA, Fungal↗

DNA damage, cytotoxic effect and cell-cycle perturbation of Hoechst 33342 on L1210 cells in vitro.

This study was designed to evaluate the effects of vital dye Hoechst 33342 (HO 33342), at concentrations used to obtain a good DNA histogram resolution, on DNA integrity, cell growth, and cell-cycle phase distribution of L1210 cells. HO 33342 exposure for 2 h, at 37 degrees C produced DNA single-strand breaks as assessed by the method of alkaline elution. DNA single-strand breaks were concentration dependent (in the range .5-5 micrograms/ml) and increased significantly when HO 33342 (0.5-1.5 micrograms/ml) was associated with exposure in a flow cytometer to U.V. laser beam illumination. HO 33342 produced a cytotoxic effect on cell growth even at the concentration of 0.5 microgram/ml--a concentration ten-fold smaller than those required to obtain a good DNA histogram resolution. HO 33342 produced a severe block of the cells in the G2-M phase of the cell cycle already evident 24 h after stain exposure and continuing up to 144 h after start of recovery. A new polyploid cell population (with a 4 c DNA content) not present in the unstained cells was already evident 24 h after dye exposure. The data shown in the present paper would imply caution in using sorted cells stained with HO 33342 dye for biological, biomedical, and pharmacological studies.

Animals↗

Analysis of simian virus 40 infection of CV-1 cells by quantitative two-color fluorescence with flow cytometry.

Quantitative two-color fluorescent analysis of Simian virus (SV40) infection of permissive CV-1 cells was investigated. Analysis included by quantitation of cellular DNA, the early viral tumor (T) antigen with a monoclonal antibody, and late viral (V) antigens with a polyclonal antibody. T antigen was detected in all phases of the cell cycle at 6 and 12 h, after SV40 infection of growth arrested cells. At later time intervals, the percentage of T-antigen-positive cells increased with the induction of the cells into successive rounds of DNA synthesis and an increase in tetraploid-polyploid cells. The amount of T antigen per cell increased as the cells entered the successive stages of the cell cycle (G0/G1----G2 + M----tetraploid S and G2 + M). The V antigen from adsorbed virus was detected immediately after infection. Synthesis of V antigen began in late S and G2 + M phases of the cell cycle. This quantitative analysis allows a definitive determination of antigen per cell in a population correlated with the cell cycle and may be useful in correlating viral and cellular events with transformation.

Animals↗

Quantitative evaluation of radiation-induced changes in sperm morphology and chromatin distribution.

Sperm head cytometry provides a useful assay for the detection of radiation-induced damage in mouse germ cells. Exposure of the gonads to radiation is known to lead to an increase of diploid and higher polyploid sperm and of sperm with head shape abnormalities. In the pilot studies reported here quantitative analysis of the total DNA content, the morphology, and the chromatin distribution of mouse sperm was performed. The goal was to evaluate the discriminative power of features derived by high resolution image cytometry in distinguishing sperm of control and irradiated mice. Our results suggest that besides the induction of the above mentioned variations in DNA content and shape of sperm head, changes of the nonhomogeneous chromatin distribution within the sperm may also be used to quantify the radiation effect on sperm cells. Whereas the chromatin distribution features show larger variations for sperm 21 days after exposure (dpr), the shape parameters seem to be more important to discriminate sperm 35 dpr. This may be explained by differentiation processes, which take place in different stages during mouse spermatogenesis.

Animals↗

Use of mouse hepatocytes for the flow cytometric determination of DNA levels of nuclei extracted from fresh tissue of hybrid larch (Larix x eurolepis Henry).

A rapid and reliable method is presented to release intact nuclei from small amounts (100 mg) of fresh plant tissue. Further, an accurate and readily accessible new standard is proposed. Both techniques have potential application for many plant systems. The system chosen as a standard (inbred mouse strain Balb/C or B6/AF1 hepatocyte nuclei) contains both diploid and polyploid cells. This system was applied in the flow cytometric determination of absolute nuclear DNA values of female gametophytes and in vitro propagated shoots of hybrid larch (Larix x eurolepis Henry). The amount of DNA in 2C nuclei of in vitro grown larch is 32.48 +/- 4.04 or 31.97 +/- 6.14 pg/nucleus, respectively, when calculated using the mouse hepatocyte 4C or 8C nuclear peak as a reference standard. The amount of DNA in female gametophyte nuclei is 17.47 +/- 1.33 pg DNA/nucleus when these haploid larch nuclei were analyzed with trout red blood cell nuclei as the standard. When hepatocyte 4C nuclei were used as a standard, the absolute value of DNA per haploid larch nucleus was estimated as 16.8 +/- 0.53 pg. Plant tissue with as little as 4-6 pg DNA/nucleus up to as much as 35 pg DNA/nucleus can be tested using mouse hepatocytes as a standard while retaining an optimal sample/standard ratio.

Animals↗

DNA content distribution of mouse cells following infection with polyoma virus.

Infection of primary to tertiary mouse embryo fibroblasts or mouse kidney cells with polyoma virus leads to stimulation of cellular DNA synthesis. When either confluent or growing mouse cells were infected, the monolayer cells were found to accumulate cells with a DNA content of S and G2/M phases of the cell cycle as assayed by flow cytometry. A similar pattern of DNA content was also observed in cells in the supernatant, which are probably cells replicating virus and dying. When compared with control cells, the infected monolayer and supernatant cells exhibited a population (5-27%) with a > G2 DNA content. The increase in DNA content of these > G2 cells was calculated to be an average of 26.7%, which is probably due to viral DNA. Polyoma contrasts with another papovavirus, SV40, which stimulates cells into DNA synthesis, with the majority of cells attaining a > G2/tetraploid DNA content, suggesting that there are differences in polyploidization between these two viruses.

Animals↗