Correlation Between Balance of Specific Chromosomes and Expression of Malignancy in Hamster Cells
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Benedict, William F.; Rucker, Natalie; Mark, Corey; Kouri, Richard E.

doi:10.1093/jnci/54.1.157

Cited by 64 publications

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“…There is, however, considerable evidence in other mammalian cell transformation systems that such is the case (20)(21)(22)(23)(24)(25). In our experiments, there is some evidence that heteroploid conversion of humah cells correlated with the acquisition of other characteristics of cell transformation.…”

Section: Discussionmentioning

confidence: 99%

Heteroploid conversion of human skin cells by methylcholanthrene.

Freeman

Lake

Igel

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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Cultured epithelial cells from human skin generally had 3-to 30-fold more hydrocarbon-metabolizing activity than fibroblasts from skin of the same donor. This activity was constant for up to 55 days in primary culture but was lost rapidly upon physical subdivision of the cultures. Treatment of primary mixed fibroblasts and epithelial cell cultures with methylcholanthrene, but not phenanthrene, led to development of actively growing fibroblastic cultures with many heteroploid cells. Unique marker chromosomes, stable over a number of cell population doublings, were identified in several of the heteroploid cell strains. Pure cultures of fibroblasts from the same donors did not undergo heteroploid conversion in response to methylcholanthrene. Spontaneously occurring heteroploidy in logarithmic phase human fibroblasts is a rare event; thus, heteroploid conversion may be a useful marker for chemical transformation of human cells. Because methylcholanthrene seems to have little transforming effect on human skin fibroblasts, human skin epithelial cells, because of their hydrocarbon-metabolizing activity, may serve to convert methylcholanthrene from a distal to an ultimate carcinogenic form.Chemically induced transformation of human cells has been difficult to achieve (1, 2) and seldom has been reported (1, 3, 4). In the two cases in which transformation was reported, the first was in diploid human cells derived from a neurofibrosarcoma (1, 3) and the second was in an aneuploid cell line established from an osteosarcoma (4). Thus, chemically induced transformation of human cells derived from nontumor tissue has not been reported.Lack of aryl hydrocarbon hydroxylase activity has been suggested as a possible mechanism whereby human fibroblasts resist transformation by carcinogenic aromatic polycyclic hydrocarbons (5). Human embryo cultures containing a high percentage of epithelial cells have been shown to have more such activity than do fibroblast cultures from the same donors (6, 7), and it has been suggested that skin epithelial cells may be the targets of choice for chemical transformation with certain classes of carcinogens (7). Human skin epithelial cells used for this purpose were found to be sensitive to the toxic effects of polycyclic hydrocarbons, but no cell transformation was noted (5-8).In this study, we have used primary human skin mixed cell cultures consisting of individual colonies containing predominantly epithelial or fibroblastic cells. Evidence is presented for clonal evolution of aneuploid populations of fibroblast cells after methylcholanthrene (MCA) treatment and for the importance of the hydrocarbon-metabolizing activity (HMA) provided by epithelial cells.MATERIALS 2451connective tissue and then minced with scissors in a small volume of growth medium [Eagle's minimum essential medium containing 1 mM sodium pyruvate, 0.1 mM nonessential amino acids, 2 mM glutamine, 100 units of penicillin per ml, 100 ,ug of streptomycin per ml, 50 ,g of kanamycin per ml, and 10% (vol/vol) heat-inactivated f...

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Section: Discussionmentioning

confidence: 99%

Heteroploid conversion of human skin cells by methylcholanthrene.

Freeman

Lake

Igel

et al. 1977

Proc. Natl. Acad. Sci. U.S.A.

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“…3), and therefore it is fair to assume that transformation in this case resulted from the action of N-methyl-Nnitrosourea. Benedict et al (1975) have shown that if the numerical balance between two groups (5 and 7) of the chromosomes of cultured Syrian hamster cells is disturbed in a particular direction, highly malignant cells result. We have shown here that an even more specific change involving the number 4 chromosome of the Chinese hamster occurs only in those subclones showving morphological evidence of transformation and the ability to grow in soft agar, two characteristics thought to be associated with malignant transformation.…”

Section: Discussionmentioning

confidence: 99%

“…Some workers have observed non-random chromosome change in tumours induced by 7,1 2-dimethylbenz(x)anthracene (AhlstrOm, 1974;Mitelman et al, 1972a, b), whereas Olinici and DiPaolo (1974) were unable to detect specific chromosome changes in tumours induced by the same chemical. Similarly, Benedict et al (1975) discovered-specific chromosome changes in Syrian hamster cell lines transformed by 1-/I-D-arabinofuranosylcytosine and dimethylnitrosamine, but other workers found no correlation between chromosome change and spontaneous transformation of rat cells (Jackson, Sanford and Dunn, 1970) or chemically induced transformation of Syrian hamster cells (DiPaolo, Popescu and Nelson, 1973).…”

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Chemical transformation of Chinese hamster cells: II. Appearance of marker chromosomes in transformed cells

Kirkland¹,

Venitt²

1976

Br J Cancer

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The chromosomes of 12 samples of cultured Chinese hamster kidney and prostate cells (4 normal and 8 transformed), whose tissue culture properties have already been described (Kirkland, 1976) have been examined for numerical change and for the appearance of abnormal markers. Six transformed kidney subclones contained a consistent telocentric marker not present in the normal parental cell, and Giemsa banding demonstrated this to be the centromere and the long (q) arm of the number 4 chromosome in all cases. Two transformed prostate subclones also contained a consistent telocentric marker, not present in similarly derived normal subclones or in the normal parental cell, and Giemsa banding demonstrated this to be a different fragment (the centromere and most of the p arm) of the number 4 chromosome. It is believed that the use of a mixed-serum culture medium, designed to stabilize the karyotype of cultured Chinese hamster cells, is at least partly responsible for the detection of these transformation-associated chromosome changes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4

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“…Indeed, cytogenetic analysis of neoplastic golden hamster cells, revertants with a suppressed malignant phenotype and segregants from these revertants which were again malignant, have led to the identification of chromosomes which control the expression and suppression of malignancy (Hitotsumachi et al, 1971(Hitotsumachi et al, ,1972Benedict et al, 1975;Bloch-Shtacher & Sachs, 1976). It has also been reported that more than one chromosome may carry genes which control malignancy in this species (Hitotsumachi et al, 1971(Hitotsumachi et al, ,1972 Yamamoto et al, 1973a, b;Bloch-Shtacher & Sachs, 1976). Some of the factors which control malignancy have also been assigned to specific chromosomes in the rat (Levan & Levan, 1975), mouse (Codish & Paul, 1974;Klein, 1979) and the Chinese hamster (BlochShtacher & Sachs, 1977).…”

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Karyotype analysis of carcinogen-treated Chinese hamster cells in vitro evolving from a normal to a malignant phenotype

Connell¹

1984

Br J Cancer

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Summary The relationship of cytogenetic changes with the acquisition of an indefinite life span in vitro, the ability of cells to grow in soft agar and their tumourigenicity in syngeneic animals has been studied in control, trans-7,8-dihydrodiolbenzo(a)pyrene and 7fl,8a-dihydroxy-9a,10a-epoxy-7,8,9,10-tetrahydrobenzo(a)-pyrenetreated secondary cultures derived from Chinese hamster embryonic lung. Karyotype analysis revealed a sequence of chromosome changes as the cells progressed through culture. Aneuploidy, namely trisomy of chromosome 4, the long arm in particular, was an early dominant change. The possible association of this trisomy with the acquisition of immortality in vitro is implicated, although the involvement of other nonrandom chromosome changes cannot be eliminated, implying that there may be several genomic sites in the Chinese hamster which may potentially be involved with the acquisition of unlimited growth potential. Neither the ability of cells to grow in soft agar nor as tumours could be associated with any specific chromosome(s). Double minutes were observed in metaphases from the cell lines, agar colonies and tumours; their possible relationship with growth advantage is discussed.Karotype abnormalities characterise the majority of metaphases recovered from malignant cells. Indeed, cytogenetic analysis of neoplastic golden hamster cells, revertants with a suppressed malignant phenotype and segregants from these revertants which were again malignant, have led to the identification of chromosomes which control the expression and suppression of malignancy (Hitotsumachi et al., 1971(Hitotsumachi et al., ,1972Benedict et al., 1975;Bloch-Shtacher & Sachs, 1976). It has also been reported that more than one chromosome may carry genes which control malignancy in this species (Hitotsumachi et al., 1971(Hitotsumachi et al., ,1972 Yamamoto et al., 1973a, b;Bloch-Shtacher & Sachs, 1976). Some of the factors which control malignancy have also been assigned to specific chromosomes in the rat (Levan & Levan, 1975), mouse (Codish & Paul, 1974;Klein, 1979) and the Chinese hamster (BlochShtacher & Sachs, 1977).The evolution of the malignant phenotype as a progressive multi-step process has been demonstrated both in vivo (Foulds, 1969(Foulds, ,1975 and in vitro (Barrett & Ts'o, 1978a, b;Barrett et al., 1980). In vitro studies have indicated that as the neoplastic phenotype evolves, the unknown series of genetic and/or epigenetic events underlying this evolutionary process are reflected through various abnormal phenotypes, i.e. the acquisition of immortality (Newbold et al., 1982) and loss of anchorage dependency for growth (Connell & Ockey, 1977;Barrett, 1979 7,B,8,9,

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Correlation Between Balance of Specific Chromosomes and Expression of Malignancy in Hamster Cells 2

Cited by 64 publications

References 0 publications

Heteroploid conversion of human skin cells by methylcholanthrene.

Heteroploid conversion of human skin cells by methylcholanthrene.

Chemical transformation of Chinese hamster cells: II. Appearance of marker chromosomes in transformed cells

Karyotype analysis of carcinogen-treated Chinese hamster cells in vitro evolving from a normal to a malignant phenotype

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