Measles associated chromosome breakage

Abstract

In 1962 we reported chromosome breaks in peripheral white blood cells (1) of patients with clinical measles (rubeola). This work was part of a study on the relationship between viruses, chromosomes, and carcinogenesis. The first system studied in this project was a tumor virus, the Schmidt-Ruppin strain of the Rous sarcoma virus. This produces tumors not only in the chicken and fowl but also in a wide variety of mammals (2). When this virus was studied in the rat it was noted that chromosome breakage occurred when the tumor was studied in vivo or in tissue culture and also when the virus was added to normal rat cells in tissue culture (3). When the chromosomes of the rat tumors induced by this virus were studied in serial transplantation, new chromosome types were seen to arise. This could only occur as the result of previous breakage and reunion or healing between the broken ends of chromosomes.When rat tumors of "0" passage were put into tissue culture and serially transferred, they underwent a cellular transformation with change in morphology and growth characteristics. At the time these cellular changes took place, large numbers of chromosome breaks and rearrangements were seen. After this, the cells stabilized and behaved as a cell line. The breaks and rearrangements had not been seen in preparations made before the morphologic transformation and have not been seen since that time. Finally, when cell-free virus was added to diploid rat embryo cells in tissue culture and the first and second divisions after the addition were studied ehromosomally, it was found that there was an increase in the number of breaks over the controls. On the basis of these observations it was felt that breakage was playing a role in the interaction of the cell and tumor virus.

Mitotic Cell Death by Chromosome Fragmentation

“…Based on the morphologic characterization, chromosome fragmentation might offer insight into the mechanism of the long-described phenomenon of chromosome pulverization (36). Frequently observed after viral infection and thought to occur from cell fusion, chromosome pulverization has often been linked to the prematurely condensed chromosomes and thus was thought of as occurring in interphase nuclei.…”

Effect of Viable and Non-viable Measles Virus on Proliferating Human Lymphocytes

“…Leukopenia and lymphopenia are com mon during active measles infection [14,15], and the virus has been cul tured from blood leukocytes during that time [16]. The studies of Ni chols et al [17,18] have shown that addition of measles virus to a varie ty of tissue cells, including human leukocytes, leads to several types of chromosomal abnormalities, particularly in proliferating cells [19], N orrby et al [20] have shown that measles virus treated in a variety of ways to render it noninfective retains several biologic characteristics, including the capacity to induce some cytopathogenic effects. Although studies uti lizing autoclaved virus were not reported by this group, preliminary in vestigations in our laboratory suggest that autoclaved preparations may retain some of the biological activities of the measles virus, although non infective.…”

Heterogeneity of Cell Death

“…MCDs also occur in response to various types of stress, often when cell cycle checkpoint function is abrogated, though they can also occur in normal tissue . C-Frag, for instance, has been shown to occur in swine lymphocytes in response to vaccination [Nichols and Levan, 1965]. It also occurs in response to chemotherapeutic treatments, gene defects, ER stress, HSP90 inhibition, genomic instability and centrosome amplification.…”