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Influence of blood pressure on development of aortic medial smooth muscle hypertrophy in spontaneously hypertensive rats.

The hypothesis that a primary stimulus for aortic medial hypertrophy in spontaneously hypertensive rats (SHR) is increased blood pressure was tested by determining whether development of smooth muscle cell hypertrophy and hyperploidy in SHR could be dissociated from blood pressure levels in rats treated with various antihypertensive drugs with different mechanisms of action. Wistar-Kyoto rats (WKY) and SHR were treated between 2 and 5 months of age with captopril (375 mg/L), hydralazine (40 mg/L), or propranolol (1.5 mg/L) administered in their drinking water. Smooth muscle hypertrophy and hyperploidy were analyzed by morphometric evaluation of medial smooth muscle content, flow cytometric analysis of the frequency of polyploid smooth muscle cells, and biochemical estimates of smooth muscle cell number. All drugs significantly lowered blood pressure in SHR compared with untreated controls (order of efficacy: captopril greater than hydralazine greater than propranolol). Captopril also was most effective at changing blood pressure in WKY, while propranolol and hydralazine had similar blood pressure-lowering effects. The efficacy of drugs in preventing the development of smooth muscle cell polyploidism and medial hypertrophy in SHR was the same as their efficacy in lowering blood pressure, although propranolol had no effect on medial smooth muscle hypertrophy despite lowering blood pressure by 26 mm Hg. Regression analyses showed a high degree of correlation between blood pressure and the frequency of polyploid smooth muscle cells and medial smooth muscle content. These results are consistent with the hypothesis that aortic medial hypertrophy may be, in part, a response to increased blood pressure or wall stress. However, analysis of covariance and two-stage multiple regression analyses indicated that captopril had an effect over and above that predicted by its blood pressure-lowering effect. Furthermore, propranolol lowered blood pressure but did not affect medial hypertrophy. These results suggest that smooth muscle hypertrophy is not simply a response to increased blood pressure, but that other factors, such as angiotensin II, may be important in modulating aortic medial hypertrophy in SHR.

Animals↗

Secretion of a unique peptide from interleukin-2-stimulated natural killer cells that induces endomitosis in immature human megakaryocytes.

When interleukin-2 (IL-2) was added to immature, low-ploidy (greater than 80% 2N+4N) megakaryocytes generated in IL-3 and stem cell factor (SCF)-containing liquid cultures of blood mononuclear cells highly enriched in hematopoietic progenitors, a 2- to 6-fold increase in the absolute number of polyploid (more than 8N) megakaryocytes was noted. This effect was found to be indirect and was mediated through natural killer (NK) cells that constitute the major lymphoid cell contaminating day 6 megakaryocyte cell populations. IL-2 had no effect on megakaryocytes generated from CD34(+) cells stimulated with IL-3 and SCF. However, medium conditioned by IL-2-stimulated, but not resting, NK cells (NKCM) contained a trypsin-sensitive factor capable of increasing 2- to 5-fold the number of polyploid megakaryocytes generated in vitro from IL-3 and SCF-stimulated CD34(+) cells. The activity in NKCM was dose dependent and could not be neutralized by an excess of antibodies to IL-6, IL-11, leukemia inhibitory factor (LIF), gp130, stromal cell derived factor-1a (SDF-1a), and thrombopoietin (TPO). Addition of IL-11, but not TPO, to NKCM-containing cultures resulted in further augmentation of polyploidy, with the generation of 50% to 70% polyploid megakaryocytes with a modal ploidy of 16N. This factor is distinct from TPO because it induces endomitosis in IL-3-generated megakaryocytes in vitro, whereas TPO does not, and its activity on megakaryocyte ploidy is not altered by optimal concentrations of TPO. In addition, no message for TPO is detectable in IL-2-stimulated NK cells by reverse transcription-polymerase chain reaction. These findings indicate that IL-2-stimulated NK cells produce a novel peptide, distinct from TPO, IL-6, IL-11, LIF, other gp130-associated interleukins, and SDF1a, that can induce in vitro endomitosis in immature human megakaryocytes in the presence of IL-3 and SCF.

Antigens, CD↗

Stem cells, senescence, neosis and self-renewal in cancer.

We describe the basic tenets of the current concepts of cancer biology, and review the recent advances on the suppressor role of senescence in tumor growth and the breakdown of this barrier during the origin of tumor growth. Senescence phenotype can be induced by (1) telomere attrition-induced senescence at the end of the cellular mitotic life span (MLS*) and (2) also by replication history-independent, accelerated senescence due to inadvertent activation of oncogenes or by exposure of cells to genotoxins. Tumor suppressor genes p53/pRB/p16INK4A and related senescence checkpoints are involved in effecting the onset of senescence. However, senescence as a tumor suppressor mechanism is a leaky process and senescent cells with mutations or epimutations in these genes escape mitotic catastrophe-induced cell death by becoming polyploid cells. These polyploid giant cells, before they die, give rise to several cells with viable genomes via nuclear budding and asymmetric cytokinesis. This mode of cell division has been termed neosis and the immediate neotic offspring the Raju cells. The latter inherit genomic instability and transiently display stem cell properties in that they differentiate into tumor cells and display extended, but, limited MLS, at the end of which they enter senescent phase and can undergo secondary/tertiary neosis to produce the next generation of Raju cells. Neosis is repeated several times during tumor growth in a non-synchronized fashion, is the mode of origin of resistant tumor growth and contributes to tumor cell heterogeneity and continuity. The main event during neosis appears to be the production of mitotically viable daughter genome after epigenetic modulation from the non-viable polyploid genome of neosis mother cell (NMC). This leads to the growth of resistant tumor cells. Since during neosis, spindle checkpoint is not activated, this may give rise to aneuploidy. Thus, tumor cells also are destined to die due to senescence, but may escape senescence due to mutations or epimutations in the senescent checkpoint pathway. A historical review of neosis-like events is presented and implications of neosis in relation to the current dogmas of cancer biology are discussed. Genesis and repetitive re-genesis of Raju cells with transient "stemness" via neosis are of vital importance to the origin and continuous growth of tumors, a process that appears to be common to all types of tumors. We suggest that unlike current anti-mitotic therapy of cancers, anti-neotic therapy would not cause undesirable side effects. We propose a rational hypothesis for the origin and progression of tumors in which neosis plays a major role in the multistep carcinogenesis in different types of cancers. We define cancers as a single disease of uncontrolled neosis due to failure of senescent checkpoint controls.

Journal Article↗

Generational variation and stabilization in resynthesized allotetraploid Brassica juncea derived from diploid progenitors B. rapa and B. nigra.

BACKGROUND: Polyploidy is a major driver of plant evolution and crop improvement, generating novel variation in morphology, physiology, and agronomic traits. Brassica juncea (AABB, 2n = 36), a natural allotetraploid derived from B. rapa (AA) and B. nigra (BB), is an important oilseed and vegetable crop; however, its narrow genetic base limits further breeding gains. Resynthesized B. juncea (RBJ), developed from known progenitors, provides a tractable system to investigate polyploid stabilization, trait diversification, and generational variation. This study evaluated RBJ across nine generations (F1-S8) to elucidate generational variation in morphological, molecular, cytological, and oil content traits during progressive stabilization. RESULTS: Substantial variation was observed for key yield-related traits, including siliqua length, seeds per siliqua, and thousand-seed weight. High estimates of heritability, genotypic variance, and genetic advance indicated their potential utility in selection based improvement. Comparative analyses revealed a clear generational progression, characterized by relatively enhanced performance in early generations, increased recombination-driven variability in intermediate generations, and the partial stabilization of several traits in later generations. Generation mean analysis suggested the involvement of additive, dominance, and epistatic gene effects in trait inheritance. Molecular analysis using SSR markers confirmed the amphidiploid origin and genomic integrity of RBJ generations. Cytological assessments, pollen viability assays, and flow cytometric analysis collectively demonstrated stable chromosome numbers, improved fertility, and maintenance of ploidy stability across successive generations. CONCLUSIONS: The study provides valuable insights into the generational variation and stabilization of morphological, molecular, and oil content traits in resynthesized B. juncea. The findings suggest that variability arising from polyploidization and interspecific hybridization undergoes gradual reorganization across successive generations, leading to increased trait stabilization and more consistent expression of selected agronomic characteristics. Collectively, these results contribute to the understanding of early stabilization processes in RBJ, highlighting resynthesized polyploids as useful systems for studying variation and stabilization in allopolyploid crops.

Mustard Plant↗

Estrogen receptor in deciduoma cells separated by velocity sedimentation.

Nuclear estrogen receptor levels were measured in fractions of dispersed deciduoma cells separated according to size by velocity sedimentation at unit gravity. Previous studies demonstrated that velocity sedimentation separated larger fully differentiated polyploid deciduoma cells from smaller diploid cells. Since levels of estrogen receptor measured in homogenates of deciduoma tissue decreased during the growth and differentiation of the deciduoma, lower levels of estrogen receptor per cell were anticipated in polyploid deciduoma cells. Although levels of estrogen receptor decreased slightly in all fractions of deciduoma cells from days 7-8 of pseudopregnancy, the larger polyploid cells had higher levels of estrogen receptor than smaller cells on both days. These results indicate that differentiation of endometrial stromal cells during decidualization involves a decrease in receptor levels in all deciduomal cell types rather than a specific decrease in the receptor levels of only fully differentiated deciduoma cells. (Endocrinology 108: 484, 1981)

Animals↗

The Drosophila gene morula inhibits mitotic functions in the endo cell cycle and the mitotic cell cycle.

In the endo cell cycle, rounds of DNA replication occur in the absence of mitosis, giving rise to polyploid or polytene cells. We show that the Drosophila morula gene is essential to maintain the absence of mitosis during the endo cycle. During oogenesis in wild-type Drosophila, nurse cells become polyploid and do not contain cyclin B protein. Nurse cells in female-sterile alleles of morula begin to become polyploid but revert to a mitotic-like state, condensing the chromosomes and forming spindles. In strong, larval lethal alleles of morula, the polytene ring gland cells also inappropriately regress into mitosis and form spindles. In addition to its role in the endo cycle, morula function is necessary for dividing cells to exit mitosis. Embryonic S-M cycles and the archetypal (G1-S-G2-M) cell cycle are both arrested in metaphase in different morula mutants. These phenotypes suggest that morula acts to block mitosis-promoting activity in both the endo cycle and at the metaphase/anaphase transition of the mitotic cycle. Consistent with this, we found cyclin B protein to be inappropriately present in morula mutant nurse cells. Thus morula serves a dual function as a cell cycle regulator that promotes exit from mitosis and maintains the absence of mitosis during the endo cycle, possibly by activating the cyclin destruction machinery.

Alleles↗

Polyploidy associated with oxidative injury attenuates proliferative potential of cells.

Polyploid cells are encountered ubiquitously but the biological significance of polyploidy is unclear. In view of their extensive capacity for regeneration, hepatocytes offer excellent systems for analyzing growth control mechanisms. We isolated hepatocytes from adult rats with and without two-third partial hepatectomy, which induces hepatic polyploidy. Polyploid hepatocytes showed evidence for oxidative injury with antioxidant depletion, lipid peroxidation and 8-hydroxy-adducts of guanine in nuclear DNA. Liver repopulation assays in intact animals showed markedly decreased replication capacity in polyploid hepatocytes. Recapitulation of polyploidy in cultured hepatocytes established that mitogenic stimulation in the presence of oxidative DNA injury was capable of inducing polyploidy. The findings provide novel frameworks in the context of polyploidy for understanding tissue development, regeneration and oncogenesis.

Animals↗

Prognostic significance of DNA ploidy and proliferative index (MIB-1 index) in childhood rhabdomyosarcoma.

The prognostic value of DNA ploidy and proliferative index (PI) are well established in many cancers, but their significance in childhood rhabdomyosarcoma (RMS) is unclear. We studied the DNA content and PI of 45 cases of childhood RMS obtained retrospectively. DNA histograms were hyperdiploid in 30 cases (67%), diploid in 6 (13%), tetraploid in 5 (11%), polyploid in 3 (7%), and nonclassifiable in 1 (2%). The 5-year overall survival rate by ploidy was 60% (3/5) in tetraploid, 57% (17/30) in hyperdiploid, and 0% in diploid and polyploid cases (P = .000002). The 5-year overall survival by a PI less than or greater than 19% was 62% (13/21) and 21% (5/24), respectively (P = .006). In multivariate analysis, DNA ploidy (P = .001) was an important independent prognostic factor. DNA content in childhood RMS is an important variable in predicting prognosis. DNA hyperdiploid and tetraploid rhabdomyosarcomas had a favorable prognosis, while DNA diploid and polyploid tumors had a poor prognosis.

Adolescent↗

Development of polyploidy in B-cells of normal and diabetic mice.

This study was designed to clarify the relationship between pancreatic B-cell polyploidization and the progress of the diabetic syndrome in genetically diabetic (C57BL/Ks-db/db) and normal control mice (C57BL/KsJ) of matched age groups. Nuclear volume was confirmed to be a proper index of the polyploid class of the B-cell by correlation with Feulgen-DNA content as measured by microdensitometry. Nuclei of B-cells, identified by aldehyde fuchsin positive cytoplasmic granules, were traced by camera lucida and their volumes determined by semiautomatic particle size analysis. Six age groups were studied: 4.5, 7, 9.5, 12, 14.5 and 17 weeks. The major conclusions are: 1) The percentage of tetraploid nuclei in normal mice is consistently between 1.0 and 2.0% from 4.5 to 14.5 weeks of age and increases to approximately 3.0% at 17 weeks of age; however, further studies are required to determined the significance of this increase; 2) in all age groups studied, percentages of polyploid nuclei are significantly greater in diabetic than in control mice; 3) the percentage of tetraploid nuclei in diabetic animals is elevated 220% over controls at 4.5 weeks of age, remains constant until 12 weeks (while other parameters such as blood glucose level and body weight continue to rise) and increases significantly between 12 and 14.5 weeks of age. Implications of both the increased polyploidy observed at the onset of disease symptoms, and the dramatic increase occurring during the later stages of the disease, are discussed.

Age Factors↗

A model selection-based interval-mapping method for autopolyploids.

While extensive progress has been made in quantitative trait locus (QTL) mapping for diploid species, similar progress in QTL mapping for polyploids has been limited due to the complex genetic architecture of polyploids. To date, QTL mapping in polyploids has focused mainly on tetraploids with dominant and/or codominant markers. Here, we extend this view to include any even ploidy level under a dominant marker system. Our approach first selects the most likely chromosomal marker configurations using a Bayesian selection criterion and then fits an interval-mapping model to each candidate. Profiles of the likelihood-ratio test statistic and the maximum-likelihood estimates (MLEs) of parameters including QTL effects are obtained via the EM algorithm. Putative QTL are then detected using a resampling-based significance threshold, and the corresponding parental configuration is identified to be the underlying parental configuration from which the data are observed. Although presented via pseudo-doubled backcross experiments, this approach can be readily extended to other breeding systems. Our method is applied to single-dose restriction fragment autotetraploid alfalfa data, and the performance is investigated through simulation studies.

Algorithms↗

Evolution and expression of homeologous loci in Tragopogon miscellus (Asteraceae), a recent and reciprocally formed allopolyploid.

On both recent and ancient time scales, polyploidy (genome doubling) has been a significant evolutionary force in plants. Here, we examined multiple individuals from reciprocally formed populations of Tragopogon miscellus, an allotetraploid that formed repeatedly within the last 80 years from the diploids T. dubius and T. pratensis. Using cDNA-AFLPs followed by genomic and cDNA cleaved amplified polymorphic sequence (CAPS) analyses, we found differences in the evolution and expression of homeologous loci in T. miscellus. Fragment variation within T. miscellus, possibly attributable to reciprocal formation, comprised 0.6% of the cDNA-AFLP bands. Genomic and cDNA CAPS analyses of 10 candidate genes revealed that only one "transcript-derived fragment" (TDF44) showed differential expression of parental homeologs in T. miscellus; the T. pratensis homeolog was preferentially expressed by most polyploids in both populations. Most of the cDNA-AFLP polymorphisms apparently resulted from loss of parental fragments in the polyploids. Importantly, changes at the genomic level have occurred stochastically among individuals within the independently formed populations. Synthetic F(1) hybrids between putative diploid progenitors are additive of their parental genomes, suggesting that polyploidization rather than hybridization induces genomic changes in Tragopogon.

DNA, Complementary↗

Microphotometric DNA analysis in moderate dysplasia of the uterine cervix. Correlation to the progression and regression of the lesion.

Nuclear DNA content was determined by microphotometry in 27 cases of moderate dysplasia of the uterine cervix. All these cases were followed from one to ten years to study the biological behavior of moderate dysplasia in relation to cervical carcinogenesis. Ten of them showed progression to carcinoma in situ during a period of one to six years (median 34.8 months) and 17 cases showed regression to inflammation and normalcy during a period of one to ten years (median 44.2 months). DNA analysis was performed both on initial cervical smear and on representative smears collected during follow-up. Amongst ten cases which progressed to malignancy, nine had aneuploid DNA pattern and one had polyploid DNA pattern throughout the follow-up period. Amongst 17 cases which regressed to inflammation, 11 had euploid and six polyploid DNA pattern. The observation that moderate dysplasia with aneuploid DNA value often develops into carcinoma in situ in contrast to dysplasia with euploid or polyploid DNA value strengthens the conception that DNA aneuploidy may be considered as 'high risk indicator' for cervical precancerous lesions.

Adult↗

Life forms protectable as subjects of U.S. patents -- microbes to animals (perhaps).

Scientists, businessmen, universities and industries with fundamental or peripheral interests in technology as applied to life processes will be keenly interested in recent U.S. Patent Office decisions. These decisions indicate that new higher life forms, animal or plant, are proper subjects of patents if they are not naturally occurring (and are not human in the case of animals). In contrast to plants and other organisms, genetically modified animals have had no mode of protection as intellectual property except possibly as a trade secret or utility patent. The Ex parte Allen decision, reached by the Patent Office Board of Appeals and Interferences, directly addressed the issue of animal patentability in view of the broad reading of 35 U.S.C. section 101 by the U.S. Supreme Court in the Chakrabarty decision. The subject invention concerned polyploid oysters. Claims directed toward polyploid oysters produced by a particular process were rejected under 35 U.S.C. section 103 and section 101. The Board, reversing the 35 U.S.C. section 101 - based rejection in view of the Chakrabarty decision, indicated that the claimed polyploid oysters were non-naturally occurring manufactures or compositions of matter within the confines of patentable subject matter under 35 U.S.C. section 101. A similar decision affecting the patentable status of plants or segments thereof had previously been reached by the Patent and Trademark Office in the case of Ex parte Hibberd, 227 U.S.P.Q. 443 (Bd. Pat. App. 1985). The Hibberd utility patent application concerned "genetically engineered" maize which had high levels of the tryptophan.

Animals↗

Phylogenetic reconstruction based on low copy DNA sequence data in an allopolyploid: the B genome of wheat.

Study of bread wheat (Triticum aestivum) may help to resolve several questions related to polyploid evolution. One such question regards the possibility that the component genomes of polyploids may themselves be polyphyletic, resulting from hybridization and introgression among different polyploid species sharing a single genome. We used the B genome of wheat as a model system to test hypotheses that bear on the monophyly or polyphyly of the individual constituent genomes. By using aneuploid wheat stocks, combined with PCR-based cloning strategies, we cloned and sequenced two single-copy-DNA sequences from each of the seven chromosomes of the wheat B genome and the homologous sequences from representatives of the five diploid species in section Sitopsis previously suggested as sister groups to the B genome. Phylogenetic comparisons of sequence data suggested that the B genome of wheat underwent a genetic bottleneck and has diverged from the diploid B genome donor. The extent of genetic diversity among the Sitopsis diploids and the failure of any of the Sitopsis species to group with the wheat B genome indicated that these species have also diverged from the ancestral B genome donor. Our results support monophyly of the wheat B genome.

Chromosome Mapping↗

Isozyme variability among cryptic species of Botrychium subgenus Botrychium (Ophioglossaceae).

The systematics of Botrychium subgenus Botrychium has been controversial, primarily because reduction in frond size and complexity has limited the number of characters available for discrimination of species. The recognition of many polyploid species has magnified the difficulty of classification because allopolyploids are often morphologically intermediate between their progenitor diploids. In order to evaluate species limits and sectional boundaries, we surveyed and compared 16 of the 24 currently recognized species for isozymic variation. Little or no intrapopulational variation was detected, but the variation present was consistent with the hypothesis that Botrychium species are primarily inbreeding. Interspecific comparisons distinguished six diploid species and provided evidence of molecular differentiation between the cryptic sister species B. lunaria and B. crenulatum. Evidence of possible progenitor/descendant relationships was found for certain diploid/polyploid relationships. Using enzyme bands shared between species, realignment of the sectional assignment of several species is proposed. Anomalous banding patterns in certain individuals suggested that gene silencing or homoeologous chromosome pairing might be operating in B. minganense, B. hesperium, and B. matricariifolium. Isozyme data also showed that some populations of species presumed to be uniformly diploid possessed isozyme patterns typical of polyploids. All available molecular data indicate that members of Botrychium subgenus Botrychium are actively evolving at diploid and polyploid levels.

Journal Article↗

Cytogeography and chromosome evolution of subgenus Tridentatae of Artemisia (Asteraceae).

The subgenus Tridentatae of Artemisia (Asteraceae: Anthemideae) is composed of 11 species of various taxonomic and geographic complexities. It is centered on Artemisia tridentata with its three widespread common subspecies and two more geographically confined ones. Meiotic chromosome counts on pollen mother cells and mitotic chromosome counts on root tips were made on 364 populations ( = 3.1 plants per population). These population counts are ∼60% of all Tridentatae counts. Some are first records for taxa. The Tridentatae are a polyploid complex (x = 9) with ploidy levels from 2x to 8x, but mostly 2x (48%) and 4x (46%). Polyploidy occurs in nine of the 11 species and in many subspecies as well. Supernumerary or b chromosomes are present only at a low frequency. In the principal species, A. tridentata, 2x plants are larger than 4x ones, which are adapted to drier conditions, probably in consequence of their slower growth rates. Gigas diploidy is a phenomenon shared by some other woody genera, but is in contrast to the gigas polyploid nature of many herbaceous genera. Polyploidy occurs within populations and is essentially autoploid. Hybridization sometimes occurs at taxa interfaces in stable hybrid zones. Stable Tridentatae hybrid zones coupled with the group's inherent propensity for polyploidization has led to the establishment of a geographically and numerically large and successful complex of species.

Journal Article↗

Protein content and number of nucleolar organizer regions are enhanced during phorbol ester-induced differentiation of cultured human megakaryocytic cells.

In order to investigate the protein synthesis in megakaryocyte polyploidization, phorbol myristate acetate (PMA, 5 x 10(-9) M), a differentiation marker known to induce megakaryocyte polyploidization, was added to human megakaryocytic cell lines (DAMI, HEL and K562) and the expression of platelet/megakaryocytic integrins, the numbers of nucleolar organizer regions (AgNORs) and the total protein content were estimated. Following exposure of PMA, the expression of the platelet membrane glycoprotein GPIIIa and thrombospondin and transferrin receptors was augmented in the three cell lines. The number of AgNORs shifted from 16.4 +/- 4.3, 24.4 +/- 2.5 and 13.6 +/- 3.1 for unstimulated cells to 20.0 +/- 5.3, 38.7 +/- 7.9 and 16.8 +/- 2.3 for PMA-treated DAMI, HEL and K562 cells, respectively. Furthermore, after treatment with PMA, the numbers of AgNORs clusters or nucleoles increased significantly to 179%, 238% and 154% of controls in DAMI, HEL and K562 cell lines, respectively. Finally, addition of PMA culture for four days, significantly increased the protein contents to 153%, 171% and 254% of controls for DAMI, HEL and K562 cell lines, respectively (p < 0.05 by t-test). In conclusion, the increase in the total protein content and in the number of AgNORs by PMA, suggests that PMA-induced-megakaryocyte polyploidization occurs by enhanced protein production.

Cell Differentiation↗

Cytophotometric studies in suspicious cervical smears.

Papanicolaou stained smears of various cervical lesions diagnosed as "suspicious" by routine cytology were reviewed with regard to different cell types leading to this diagnosis. The smears were then submitted to Feulgen hydrolysis and redyed by Acriflavin-SO2 for fluorescence-cytophotometry. In nine of 14 cases measured, the DNA content of all types of "suspicious" cells was increased with DNA modes at euploid levels of 2 n, 4 n and 8 n indicating that the "suspicious" cells in those cases are polyploid. However, in five cases aneuploid DNA-distribution patterns were found similar to those observed in carcinoma in situ or severe dysplasia. Since polyploidization may be considered as a cellular response to higher functional requirement (i.e. inflammation or regeneration) a "suspicious" cervical smear with a polyploid DNA-distribution pattern may reverse to normal cervical epithelium after normal conditions are restored. However, a "suspicious" smear with an aneuploid DNA-distribution pattern should be considered more seriously as being related to a precancerous lesion requiring immediate surgical treatment.

Aneuploidy↗