PubMed Health⌕ Search

Biomedical subjects

A B Mukherjee

Publications and source records attributed to A B Mukherjee.

At least 37 records · Page 2Linked to original sources
PubMed1998

Chromium in the environment of Finland.

This paper focuses upon the use, import and release of chromium to the environment of Finland. In addition, the behavior of trivalent and hexavalent chromium in soils has been briefly reviewed. In Finland, consumption of chromium compounds occurs in the following pattern: stainless steel > leather tanning > metal plating > chemicals. The emission of chromium has decreased from 114 t in 1979 to 28 t in 1995. The highest release of chromium continues to be from ferrochromium and stainless steel plants. From these facilities, 85% of slag and dusts are used by a secondary facility to recover valuable metal. In the industrial areas, the oxidizing behavior of chromium (III) is still unknown. In this study, the leachability of chromium (VI) to ground water and its effects on terrestrial and aquatic species in Finland are discussed.

Chromium↗
PubMed1998

Aneuploidy analysis in fibroblasts of human premature aging syndromes by FISH during in vitro cellular aging.

Cultured cells from human premature aging syndromes show premature replicative senescence and as such might serve as models for genetic studies of cellular replicative senescence/aging. To date, no systematic study on chromosome-specific aneuploidy in premature aging syndromes has been carried out using molecular-cytogenetic techniques. We, therefore, have performed a comparative analysis of chromosome-specific aneuploidy levels at both interphase and metaphase in earlier (younger) and later (older) passage fibroblasts from two normal male and female versus six male and female premature aging syndromes (Cockayne, Hutchinson-Gilford and Werner) by FISH. We have used seven chromosome-specific DNA probes (nos. 1, 4, 6, 8, 10, 15, X) and four DNA probes (nos. 1, 4, 6, X) for females and males, respectively. Our data on total aneuploidy of each chromosome in all cell cultures indicated that significantly higher percentages of aneuploid cells were detectable at interphase than at metaphase. Also, the interphase aneuploidy levels of all chromosomes under study were significantly higher in cells from the syndromes as compared to these of the normal controls at both earlier and later passages. In general, the interphase aneuploidy level of each of the chromosomes in both the control and experimental cell cultures increased with in vitro proliferation and aging, although to a much lesser extent in the controls. The aneuploidy levels, however, varied widely from chromosome to chromosome in each case. Since adequate numbers of mitotic cells were not always available in some later passage cells of various premature aging syndromes, metaphase chromosome analysis for all chromosomes under study was not always possible at this stage, but interphase cytogenetics was very informative in all cases. No consistent pattern of chromosome-specific aneuploidy was detected in the earlier passage cells (younger cells) of the syndromes. However, the later passage cells (older cells) from all three female syndromes consistently showed the highest aneuploidy levels for the X chromosome at interphase.

Adolescent↗
PubMed1998

Uteroglobin: physiological role in normal glomerular function uncovered by targeted disruption of the uteroglobin gene in mice.

Blastokinin or uteroglobin (UG) is an evolutionarilly conserved, steroid-inducible, homodimeric, multifunctional, secreted protein with potent Immunomodulatory/antiinflammatory properties. Recently, a UG-receptor expressed on several malignant and normal cell types has been characterized. Although the biochemistry, structural, and molecular biology of UG have been extensively studied, its physiological function(s), until recently, remained unknown. By generating UG-null (UG-/-) mice, we determined that an essential role of UG is to prevent severe renal disease caused by an abnormal deposition of predominantly multimeric fibronectin (Fn) and collagen in the glomerulus. The molecular mechanisms by which UG prevents this disease in control (UG+/+) mice, at least in part, is attributable to its high-affinity binding to Fn and the formation of Fn-UG heteromers, which counteract both Fn-Fn and Fn-collagen interactions, required for abnormal tissue deposition. In addition, by inhibiting secretory phospholipase A2 (sPLA2) activity and decreasing the level of lysophosphatidic acid (LPA), UG may indirectly prevent the activation of integrins (eg, alpha5beta1) that enhance abnormal tissue deposition of Fn. The mechanism(s) of UG action is likely to be even more complex, because it also functions through a receptor-mediated pathway that has not yet been clearly defined. Nevertheless, the UG gene-knockout mice provide a valuable animal model for investigation of human glomerulopathies in general and familial Fn-deposit glomerulopathy in particular.

Animals↗
PubMed1997

A longitudinal study of human age-related chromosomal analysis in skin fibroblasts.

Previous chromosomal analyses related to human aging used mainly cross-sectional data on metaphase chromosomes. However, it is difficult to directly relate the cross-sectional results to the specific type(s) of chromosomal mutations possibly occurring within a specific individual with advancing age, because the unique genetic endowment of each individual for longevity might be a modulating factor. We therefore have performed, for the first time, a longitudinal study of both numerical and structural chromosome analyses of skin fibroblasts at interphase and at metaphase derived from eight donors participating in the Baltimore Longitudinal Study. We have used the FISH method with chromosome-specific DNA probes and the data on total aneuploidy of 17 different chromosomes in each of the 16 cell cultures (2 from each of eight individuals) indicate that significantly higher percentages of aneuploid cells are detected at interphase than at metaphase. Mostly, the levels of chromosome-specific aneuploidy increase with the donor's advancing age and, in most individuals, chromosomes 1, 4, 6, 8, 10, and 15 show significantly higher frequencies of aneuploidy at interphase than those of the 11 other chromosomes studied. Although the significance of relatively higher levels of aneuploidy of certain chromosomes with aging remains unclear, it is intriguing to note that some of these chromosomes, such as 1, 4, and 6, have already been assigned to harbor senescence genes and chromosome 8 is known to house the gene for Werner Syndrome (progeroid syndrome), which shows very limited proliferative capacity of fibroblasts. It is conceivable that the degree and/or type of chromosome-specific aneuploidy might have some gene dosage effects in the control of cellular proliferation and selection during aging. We also show that a combination of both interphase and metaphase aneuploidy analyses provides more comprehensive and insightful information on intraindividual cellular dynamics and chromosomal aneuploidy as a function of age. Occasionally, very small proportions of cells in two individuals showed age-related structural chromosome aberrations, such as an acentric fragment derived from an X chromosome and an achromatic gap in chromosome 7. Thus, a comparative analysis of both intra- and interindividual longitudinal studies is very useful in detecting the pattern(s) of chromosome-specific alterations with increasing age.

Adult↗
PubMed1997

Potential roles of osteopontin and alphaVbeta3 integrin in the development of coronary artery restenosis after angioplasty.

Angioplasty procedures are increasingly used to reestablish blood flow in blocked atherosclerotic coronary arteries. A serious complication of these procedures is reocclusion (restenosis), which occurs in 30-50% of patients. Migration of coronary artery smooth muscle cells (CASMCs) to the site of injury caused by angioplasty and subsequent proliferation are suggested mechanisms of reocclusion. Using both cultured human CASMCs and coronary atherectomy tissues, we studied the roles of osteopontin (OPN) and one of its receptors, alphavbeta3 integrin, in the pathogenesis of coronary restenosis. We also measured the plasma levels of OPN before and after angioplasty and determined the effect of exogenous OPN on CASMC migration, extracellular matrix invasion, and proliferation. We found that cultured CASMCs during log phase of growth and smooth muscle cell layer of the coronary atherosclerotic tissues of patients express both OPN mRNA and protein at a significantly elevated level compared with controls. Interestingly, whereas the baseline plasma OPN levels in control samples were virtually undetectable, those in patient plasma were remarkably high. We also found that interaction of OPN with alphavbeta3 integrin, expressed on CASMCs, causes migration, extracellular matrix invasion, and proliferation. These effects were abolished when OPN or alphavbeta3 integrin gene expression in CASMCs was inhibited by specific antisense S-oligonucleotide treatment or OPN-alphavbeta3 interaction was blocked by treatment of CASMCs with antibodies against OPN or alphavbeta3 integrin. Our results demonstrate that OPN and alphavbeta3 integrin play critical roles in regulating cellular functions deemed essential for restenosis. In addition, these results raise the possibility that transient inhibition of OPN gene expression or blocking of OPN-alphavbeta3 interaction may provide a therapeutic approach to preventing restenosis.

Adolescent↗
PubMed1997

Severe fibronectin-deposit renal glomerular disease in mice lacking uteroglobin.

Despite myriads of biological activities ascribed to uteroglobin (UG), a steroid-inducible secreted protein, its physiological functions are unknown. Mice in which the uteroglobin gene was disrupted had severe renal disease that was associated with massive glomerular deposition of predominantly multimeric fibronectin (Fn). The molecular mechanism that normally prevents Fn deposition appears to involve high-affinity binding of UG with Fn to form Fn-UG heteromers that counteract Fn self-aggregation, which is required for abnormal tissue deposition. Thus, UG is essential for maintaining normal renal function in mice, which raises the possibility that an analogous pathogenic mechanism may underlie genetic Fn-deposit human glomerular disease.

Animals↗
PubMed1997

Altered sialylation of osteopontin prevents its receptor-mediated binding on the surface of oncogenically transformed tsB77 cells.

It has been reported previously that oncogenically transformed cells secrete different molecular forms of osteopontin (OPN), a sialic acid-rich, adhesive, phosphoglycoprotein, than OPNs secreted by their nontransformed counterparts. However, the origin of the OPN isoform secreted by the transformed cells and whether it has different physiological properties which may serve transformation-specific functions remain poorly understood. Here, we report that Rat-1 cells transformed by a temperature-sensitive mutant of Rous sarcoma virus (tsB77) secrete two discrete molecular forms of OPN, a 69-kDa OPN at the nonpermissive temperature (41 degrees C) and a 62-kDa form at the permissive temperature (34 degrees C). However, tsB77 cells at both temperatures transcribe a single 1.6 kb OPN mRNA and contain only the 69-kDa form of OPN intracellularly, suggesting that the 69-kDa OPN is modified to the 62-kDa form prior to or immediately after secretion by cells at 34 degrees C. We ruled out proteolytic cleavage, differential phosphorylation, or lack of N- or O-linked carbohydrates as the possible mechanism, but found that the 62-kDa OPN contains significantly reduced levels of sialic acid, as compared to its 69-kDa form. The binding assays using 32P-labeled OPN revealed that only the 69-kDa OPN, not its 62-kDa form, undergoes receptor-mediated localization on the cell surface, although tsB77 cells synthesize OPN receptors (alpha(v)beta3 integrins) at both permissive and nonpermissive temperatures. Furthermore, 125I-labeled purified milk OPN, which is highly sialylated and shows cell surface binding, upon digestion with neuraminidase failed to interact with the cell surface. Taken together, these results suggest that the difference between the 69-kDa and 62-kDa isoforms of OPN resides in their sialic acid content, and sialylation of OPN is crucial for its receptor-mediated binding on tsB77 cells. The data presented here demonstrate for the first time a physiological role of sialic acids in this protein, and raise the possibility that oncogenically transformed tsB77 cells may exploit the lack of OPN-receptor interactions for their invasive behavior.

Animals↗
PubMed1997

Evidence that porcine pancreatic phospholipase A2 via its high affinity receptor stimulates extracellular matrix invasion by normal and cancer cells.

Cellular migration and extracellular matrix (ECM) invasion are some of the critical steps in embryonic implantation, inflammation, wound healing, and cancer metastasis. Extracellular phospholipases A2 (PLA2s), belonging to either group I (PLA2-I) or group II (PLA2-II), play an essential role in the generation of proinflammatory lipid mediators (e.g. prostaglandins, leukotrienes, etc.). Recent reports indicate that PLA2-I, in addition to its digestive function, has receptor-mediated effects. For instance, PLA2-I, via its receptor, can induce cell proliferation and airway as well as vascular smooth muscle contraction. Here, we report that both porcine pancreatic and Naja naja PLA2s, in a dose-dependent manner, stimulate dramatic invasion of an artificial ECM (MatrigelTM) by NIH 3T3, mouse fibrosarcoma, and sarcoma cells in vitro, but it has no such effect on lymphoma and mastocytoma cells. That this is a receptor-mediated process is strongly suggested by the following findings. (a) While NIH 3T3, mouse fibrosarcoma, and sarcoma cells, which respond to PLA2-I stimulation, express high affinity PLA2-I receptor mRNA and protein, this receptor expression is not detectable in nonresponder lymphoma and mastocytoma cells. (b) There is a close correlation between the Kd values for 125I-PLA2-I binding to its receptor and the ED50 values for PLA2-I-induced ECM-invasion. (c) Catalytically inactivated PLA2-I is as effective as the active enzyme in stimulating invasion. (d) Suppression of PLA2-I receptor expression in responder cells causes inhibition of ECM invasion. (e) Treatment of the same cells with PLA2-I receptor-antibody also produces virtually identical effects. Taken together, our results identify a novel receptor-mediated function of PLA2-I and raises the possibility that extracellular PLA2s play important physiological as well as pathological roles via this receptor. To our knowledge, this is the first report of this novel receptor-mediated effect (i.e. ECM invasion) of PLA2-I on normal as well as malignant cancer cells.

3T3 Cells↗
PubMed1997

Resonance assignment and secondary structure determination and stability of the recombinant human uteroglobin with heteronuclear multidimensional NMR.

Human uteroglobin (h-UG) or Clara cell 10kDa (cc10kDa) is a steroid-dependent, 17 kDa homodimeric, secretory protein with potent anti-inflammatory/immunomodulatory properties. However, the exact physiological role still remains to be determined. It has been hypothesised that its activity is exerted through the binding of a specific target represented by a small molecule (still unknown), and that the binding is regulated by the formation/disruption of two cysteine bonds. The binding properties of the reduced UG have been proved in vitro for several different molecules, but no in vivo data are available to date. However, binding has been observed between reduced rabbit UG and a protein of an apparent molecular mass of 90 kDa and, more recently, we found an h-UG-binding protein

Animals↗
PubMed1997

Human uteroglobin gene: structure, subchromosomal localization, and polymorphism.

Human uteroglobin (hUG) or Clara cell 10-kD protein (cc10 kDa) is a steroid-dependent, immunomodulatory, cytokine-like protein. It is secreted by mucosal epithelial cells of all vertebrates studied. The cDNA encoding hUG and the 5' promoter region of the gene have been characterized previously. Here, we report that the structure of the entire hUG gene is virtually identical to those of rabbit, rat, and mouse. It is localized on human chromosome 11q12.3-13.1, a region in which several important candidate disease genes have been mapped by linkage analyses. Our data indicate that candidate genes for atopic (allergic) asthma and Best's vitelliform macular dystrophy are in closest proximity to the hUG gene. To determine whether hUG gene mutation may be involved in the pathogenesis of these diseases, we studied two isolated groups of patients, each afflicted with either atopy or Best's disease, respectively. We detected a single base-pair change in the hUG gene in Best's disease patients and normal controls but no such change was detected in atopy patients. This alteration in hUG gene-sequence in Best disease family appears to be a polymorphism. Although the results of our investigation did not uncover mutations in hUG gene that could be causally related to the pathogenesis of either of these diseases, its conservation throughout vertebrate phyla implies that this gene is of physiological importance. Moreover, the close proximity of this gene to several candidate disease genes makes it an important chromosomal marker in cloning and characterization of those genes.

Animals↗
PubMed1997

Cystic fibrosis gene mutation (deltaF508) is associated with an intrinsic abnormality in Ca2+-induced arachidonic acid release by epithelial cells.

The mechanism(s) of chronic airway inflammation in cystic fibrosis (CF) remains poorly understood. We studied Ca2+-induced release of arachidonic acid (AA), a precursor of proinflammatory lipid mediators, in epithelial cell lines with the deltaF508 mutation in CF transmembrane conductance regulator (CFTR) gene and in those lacking this mutation or cells in which this mutation was corrected by a functional CFTR gene transfer. We found that: (i) the mutant cells manifested an abnormally high Ca2+-induced AA release as compared to controls, (ii) AA release appeared to be catalyzed by a phospholipase A2 (PLA2) but not by phospholipase C followed by diacylglycerol lipase, and (iii) either correction of the CFTR-mutation or inhibition of PLA2 activity rectified this AA release abnormality. Taken together, our results suggest that CFTR mutation is associated with an intrinsic abnormality in AA release by epithelial cells carrying the deltaF508 mutation and suggest that the mechanism of chronic airway inflammation in CF, at least in part, involves this abnormality. These results also partly explain the effectiveness of high-dose ibuprofen therapy in arresting the progression of destructive lung disease in CF. Furthermore, they raise the possibility that correction of abnormal AA release by inhibiting PLA2 activity may improve the therapeutic benefits of ibuprofen.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1996

A longitudinal study of human age-related ribosomal RNA gene activity as detected by silver-stained NORs.

The relative frequencies of silver-stained nucleolar organizing regions (Ag-NORs) as a function of age have been analyzed in skin fibroblasts derived from eight adult individuals participating in the Gerontology Research Center (GRO) Longitudinal Study, NIA, Baltimore, MD. Since silver staining of NORs is correlated with rRNA gene activity, we used this cytological method to examine the pattern of rRNA gene activity in specific individuals, each at two different ages. Our results show that the average number of Ag-NORs/cell decreases significantly with advancing age of each individual, presumably indicating a general pattern of age-related decline/alteration in rRNA gene activity and this pattern is individual-specific. The findings of our longitudinal study is consistent with the results of previous cross-sectional (population) studies on rRNA gene activity as detected by Ag-NORs. However, it appears that the relative rate in the age-related decline of rRNA gene activity, as evidenced by lower Ag-NOR frequencies with age, is variable from person to person.

Adult↗
PubMed1996

Age-related aneuploidy analysis of human blood cells in vivo by fluorescence in situ hybridization (FISH).

All prior studies on human age-related chromosomal analysis were done using only metaphase figures derived from lymphocyte cultures in vitro. However, we believe that this procedure may provide only partial information, since the chromosomal abnormalities probably hidden in non-dividing and/or terminally differentiated leukocytes will not be detected by this method. We, therefore, have attempted to analyze the nature and extent of chromosome-specific aneuploidy at interphase by fluorescence in situ hybridization (FISH) in differentiated myeloid cells in vivo derived from various age-group people. Our data from an analysis of 30,032 cells derived from 12 healthy donors indicate that there is an increase in the mean percentages of myeloid cells with chromosome-specific aneuploidy in the older groups as opposed to that of the younger groups. This increase is applicable to all the three cell types examined (promyelocytes, metamyelocytes and polymorphs). In both the younger and older females, the relatively higher mean frequencies of cells with aneuploidy were noted for chromosome nos. 4, 6 and the X, whereas the lowest mean frequencies of cells with aneuploidy were consistently observed for chromosome no. 3. In the younger and older male donors, similar to the female donors except the X chromosome the higher percentages of aneuploid cells were observed for chromosome nos. 4 and 6 whereas the lowest mean frequencies of aneuploid cells were noted for chromosome no. 3. Among the five autosomes studied, chromosome no. 3 consistently yielded the lowest frequency of aneuploidy in all the three cell types derived from both the younger and older groups of males and females. This could presumably mean that the maintenance of a very high frequency of cells with disomy for chromosome no. 3 might be more beneficial for the process of survival and/or differentiation of myeloid cells as compared to that of other autosomes such as chromosome nos. 4 and 6. Among the five autosomes studied, chromosome no. I exhibited the highest rate of increment in the aneuploidy values of both males and females with advancing age.

Adult↗
PubMed1996

Cells in vivo and in vitro from osteopetrotic mice homozygous for c-src disruption show suppression of synthesis of osteopontin, a multifunctional extracellular matrix protein.

Mice carrying homozygous disruption of the c-src proto-oncogene (Src-/-) develop osteopetrosis due to an impaired ability of osteoclasts to adhere to the bone surface and/or to form bone-resorbing ruffled border. It has also been reported that osteopontin (OPN), a secreted phosphoprotein, mediates osteoclast adherence to the bone matrix. We report here that cells from Src-/- mice, both in vitro and in vivo, express OPN mRNA and protein at a significantly reduced level as compared to cells from Src+/- and +/+ animals, suggesting a potential role for the proto-oncogene c-src in the regulation of OPN gene expression. Our data also show that OPN gene expression can be induced by treatment of SR-/- cells with epidermal growth factor (EGF) and 12-O-tetradecanoyl phorbol-13-acetate (TPA). Results obtained from studies using inhibitors of receptor tyrosine kinases (RTKs) and protein kinase C (PKC) suggest that PKC and RTK are positioned in a pathway with PKC as the downstream effector for the EGF-induced OPN gene expression in SRC-/- cells, and that pp60c-src and EGF may regulate OPN gene expression through a common signalling pathway. Furthermore, contrary to published reports, our study shows that EGF-mediated cell signalling does not require functional interaction between the EGF-receptor and pp60c-src.

3T3 Cells↗
PubMed1996

Recombinant human uteroglobin suppresses cellular invasiveness via a novel class of high-affinity cell surface binding site.

The mechanism(s) that regulates invasion of trophoblasts through the uterine epithelium during embryo implantation and nidation in hemochorial placental mammals is poorly understood. While limited trophoblast invasion is essential for the establishment of normal pregnancy, dysregulation of this process may contribute to the pathogenesis of choriocarcinoma, a highly invasive and lethal form of cancer arising from the trophoblasts. We have previously demonstrated that rabbit uteroglobin (UG), a cytokine-like, antiinflammatory protein, produced by the endometrial epithelium during pregnancy, has a potent antichemotactic effect on neutrophils and monocytes in vitro. Here, we report that recombinant human UG (hUG) dramatically suppresses invasion of human trophoblasts and NIH 3T3 cells through an artificial basement membrane (Matrigel) in vitro but has no effect on that of human choriocarcinoma cells. We identified a previously unreported high-affinity, high molecular weight (approximately 190 kDa), nonglycosylated hUG-binding protein, readily detectable on human trophoblasts and NIH 3T3 cells but totally lacking on choriocarcinoma cells. Taken together, these results raise the possibility that (i) hUG plays a critical role in regulating cellular invasiveness, at least in part, via its previously unrecognized cell surface binding site, and (ii) some of the numerous biological activities of proteins of the UG family, reported so far, may be mediated via this binding site.

3T3 Cells↗
PubMed1995

Expression of antisense osteopontin RNA inhibits tumor promoter-induced neoplastic transformation of mouse JB6 epidermal cells.

Elevated expression of osteopontin (OPN), a secreted adhesive phosphoglycoprotein, is frequently associated with many transformed cell lines of epithelial and stromal origin. Moreover, several clonal lines of preneoplastic JB6 cells derived from Balb/c mouse epidermal cultures (Colburn et al., 1978, 1979), upon treatment with 12-O-tetradecanoyl phorbol-13-acetate (TPA), become irreversibly oncogenic and concomitantly synthesize OPN at elevated levels (Smith and Denhardt, 1989). In the present study we sought to determine whether OPN expression facilitates transformation of such preneoplastic (initiated) cells. We transfected TPA-promotable JB6 c141.5a cells with an expression vector containing mouse OPN cDNA in antisense orientation under transcriptional control of dexamethasone-inducible MMTV-LTR promoter. Four stably transfected clones, which expressed drastically reduced levels of OPN in the presence of both dexamethasone and TPA, were characterized. We found that (a) more than 20 copies of OPN antisense cDNA were stably incorporated into the genome of cells from two of these clones that were examined by Southern blot analysis; (b) dexamethasone-induced expression of antisense OPN RNA prevented augmented OPN expression at both mRNA and protein levels following TPA treatment; and (c) cells from all four clones failed to form colonies in soft agar medium containing both dexamethasone and TPA. Taken together, these data demonstrate that inhibition of elevated OPN expression blocks TPA-induced anchorage-independent growth of JB6 c141.5a cells, suggesting the possibility that OPN overproduction is causally related to transformation of preneoplastic cells.

Animals↗
PubMed1995

Chromosomal analysis in young vs. senescent human fibroblasts by fluorescence in situ hybridization: a selection hypothesis.

Almost all previous studies on chromosomal analysis related to in vitro aging of human fibroblasts were done using only metaphase chromosomes. However, this procedure may provide only partial information since the aneuploidy presumably hidden in interphase cells would remain undetected. For this reason, we have analyzed aneuploidy both at interphase and at metaphase. Female (IMR-90) and male (IMR-91) cells were grown from the lowest to the highest population doubling levels and aneuploidy analysis was done by FISH with alpha-satellite DNA probes of 15 autosomes and two sex chromosomes. Our data on total aneuploidy in young cells indicate that significantly higher proportions of cells with aneuploidy can be detected at interphase than at metaphase. This presumably indicates that during active division of young cells, more aneuploid than diploid cells are selected against entry to mitosis. In contrast, interphase senescent cells from both strains show significantly fewer aneuploid nuclei than do young cells at interphase. This probably indicates that during senescence, there is greater selective pressure in the culture against long-term survival of aneuploid cells than against survival of diploid cells. Our study shows that cellular dynamics with respect to aneuploidy involving various chromosomes differs significantly at interphase and at mitosis during in vitro aging of human fibroblasts, and we propose a 'Selection Hypothesis' as an explanation to our findings.

Aneuploidy↗