Transformation Of Tissue Culture Cells By Sv 40 Viruses

Simian virus 40 gained notoriety in the 1960s because it was found to be a contaminant of polio and adenovirus vaccines that had been administered to millions of healthy individuals worldwide. The public health implications of this revelation provided the initial impetus for an in-depth study of SV40 biology. Later work showed that SV40 DNA sequences as well as infectious virus are in fact found in human tumors and may have contributed to oncog- esis. It also turned out that SV40 uses mostly cellular machinery to carry out many steps in viral infection, which makes it a powerful probe for examining many fundamental questions in eukaryotic molecular biology. SV40 Pro- cols consolidates a number of well-tested step-by-step techniques in one v- ume; experts with hands-on experience in particular methods give detailed accounts of their optimized experimental protocols, so that the beginner, as well as more experienced researchers, may readily overcome problems of ambiguity often present in the literature. As with other DNA tumor viruses, the response of cultured cells to SV40 infection depends upon the species being infected. Monkey cells s- port virus production, which leads to their death, whereas rodent cells p- duce only the early proteins and acquire a transformed phenotype. Thus, SV40 Protocols is organized in two sections. The first relates to assays of the lytic cycle of the virus, and the second deals with transformation.

A. Definitions of Transformation in vitro When normal tissues or organs are explanted to conditions favoring the growth of cells as individual units ("cell culture"), the original cell population undergoes a large variety of modifications. Only a minority of the cells will thrive and multiply and within a rather short period of time, the complex composition of the original explant is replaced by a much simplified one of only a few recogniz ably different cell types. With most organs fibroblast-like cells survive longest and outgrow other types. This is then a stable state of affairs for many gener ations. This treatise will not discuss whether this simplification and stabilization represents selection of certain pre-existing cell types or a modification of cells into only a few recognizably different categories; for an excellent review see HARRIS. (1964). Table 1. Terminology Employed to Describe Transformations in vitro Type of transformation Essential features Irregular growth Lack of contact inhibition of cell membrane movement ("ruffled membranes") between juxtaposed cells Unrestrained growth Deficient inhibition of the cell cycle (mitosis) in a crowded culture Infinite growth Capacity of cells to undergo an infinite number of di visions (formation of established cell lines) Cells may depart from this typical behavior in numerous ways involving for instance cellular morphology, immunology, chromosomes or metabolism. Such changes have, sometimes rather vaguely, been called "transformations". This is unprecise and the term "transformation" will here be used exclusively to indicate disturbances in cell growth related to neoplasia.

The position of "Cancer Teaching Coordinator" at The University of Chicago has been a consistently rewarding one because of the enthusiasm and support of the faculty and the students. This volume is the result of the second of two recent intensive teach ing sessions which have been planned and implemented by the group which forms the Cancer Coordinator's Advisory Committee. The first of these teaching sessions was held in early March of 1964 and was entitled "LEUKEMIA, A Current and Forward Look. " It attracted overflow attendance from the students and staff of this medical institution augmented by members of the other medical centers in Chicago. It was a stimulating and instructive colloquium, and the only regret we heard expressed afterward was that we had not arranged for publication of the many excellent presentations. One of the events commemorating the seventy-fifth anniversary of the founding of The University of Chicago was this symposium on malignant transformations. This time the Committee advised us to plan on speedy publication, and, logically, it chose Dr. Werner Kirsten, a member of our faculty and an active and effective investigator in this general field of endeavor, to serve as editor of the volume. Again, two of the same ingredients for effective instruction were blended: an excellent group of scientists presenting their latest work and a fine, attentive audience of students and staff.

Viruses are the agent responsible for perhaps up to one million cases of cancer worldwide each year. Significantly, the study of viruses has also provided important clues to the causes and development of the most common human cancers. This volume presents an account of those viruses which have been directly associated with common human malignancies such as human papillomavirus (HPV), cervical carcinoma, Epstein-Barr virus (EBV) and Burkitt's lymphoma. In addition, the biology and biochemistry of those viruses which have been shown to be capable of transforming cells in culture are described in detail. Thus adenovirus are discussed, as are the other small DNA tumour viruses - Simian virus 40 (SV40) and polyoma virus. Consideration has also been given to human T-cell leukaemia virus (HTLV), hepatitis B virus (HBV) and human herpes virus 8 (HHV8), amongst others. General themes such as the host's immune response to viral infection, virally-induced apoptosis and the use of viruses as a delivery system in gene therapy have been discussed. Individual chapters have been written by an international group of experts in their own field of research.

Viral Transformation and Endogenous Viruses is a collection of papers presented at the symposium on ""Viral Transformation and Endogenous Viruses"" held at Vanderbilt University on April 1-2, 1974. Contributors discuss the viral function(s) responsible for the transformation of the cells that are infected with oncogenic viruses, emphasizing the type of changes that characterize transformed cells and the regulatory mechanisms that are altered after malignant transformations. This volume is organized into 10 chapters and begins with an overview of DNA-containing tumor viruses, particularly Simian Virus 40 (SV40) and its mutants with DNA deletions, insertions, and duplications. The integration and transcription of adenovirus DNA is considered, along with the characteristics of temperature-sensitive mutants of these viruses. The reader is then introduced to the chemistry and biology of RNA-containing tumor viruses, which are useful reagents to study neoplastic transformation both in vivo and in vitro. A major aspect of these viruses concerns the analysis of their genome at the chemical and genetic levels. The last part of the book is devoted to biochemical and genetic analyses of endogenous viruses isolated from avian cells. This book is a valuable resource for scientists and investigators in fields such as pathology, molecular virology, molecular biology, microbiology, oncology, and biochemistry.