Primary Mesothelial Cell Lines

Primary cultures of mesothelial cells have been established from rats, rabbits,
mice, and humans (Table 5.1). Mesothelial cell lines provide several advantages
for experimental studies: they provide a large number of cells isolated from a
single donor, cell lines can be isolated from genetically engineered mice, and
primary cell lines limit the number of animals required for experiments.
However, cell lines have several disadvantages: variability among donors,
variability in culture conditions in different laboratories, potential
phenotypic and genetic instability, and a limited life span in vitro (reviewed
in ref. 1). Some of these disadvantages can be overcome by quality control
procedures. For example, cell lines should not be passaged indefinitely; frozen
stocks should be maintained and thawed at regular intervals to prevent
phenotypic and genetic instability (reviewed in ref. 2). As in all cell cul¬ture
models, precautions are required to prevent cross-contamination and
contamination with bacteria or viruses. DNA profiles could be use¬ful to
identify cell lines; for example Manning et al (3) established initial genetic
profiles for their panel of human malignant mesothelioma cell lines. All
cultures should be screened for Mycoplasma and other pathogens (2).

(more…)

In Vivo Models of Mesothelioma, Their Purposes, and
Roles

Knowledge of the factors and mechanisms responsible for cancer induc¬tion rests
largely on the development of animal models. In these models, both benign and
malignant tumors, as well as preneoplastic lesions, can be induced by proper
experimental designs and with appropriate con¬trols, and their analogy to human
pathology can be determined. The animal models can be used to test and identify
agents (chemical, physi¬cal, or biologic) that are capable of carcinogenic
activity, and to investi¬gate their mechanisms. In addition, species and strains
of laboratory animals with specific genetic susceptibility to specific types of
sponta¬neous or induced tumors can be identified. Recently, genetic
manipula¬tion has given rise to transgenic or gene-deleted (knockout) animals,
which can reveal selective molecular pathways to carcinogenesis.

The study of in vivo animal models of carcinogenesis has sometimes followed the
indications of the evidence derived from studies of human epidemiology,
especially for occupational and environmental carcino¬gens. On the other hand,
with the systematic development of animal bioassays, many experimentally
identified active carcinogens have been subsequently shown to be human
carcinogens in epidemiologic studies.
(more…)

SV40-Mediated Oncogenesis

Maurizio Bocchetta and Michele Carbone

Simian virus 40 (SV40) was first isolated in 1958 among other simian viruses
from contaminated polio vaccine preparations, which were inadvertently
administered to millions of people in different countries from 1954 to 1963.
Soon after SV40 was introduced to the scientific com¬munity (1) its capabilities
to induce different forms of cancer in exper¬imental animals were recognized
(2,3). However, epidemiology failed to establish a conclusive link between the
administration of SV40-contaminated polio vaccines to humans and the development
of cancer (4–8). Because epidemiology was inconclusive, SV40 has been
consid¬ered for many years to be harmless to humans. From the 1970s, throughout
the 1980s, and until recently, SV40 has been utilized mainly as a tool to
understand key molecular processes such as DNA replica¬tion, splicing, and
translation in mammalian cells. It has also been widely used to uncover the
process of the cell cycle control because of the interaction of its major
oncogenic protein products with critical tumor suppressor gene pathways of the
cell. Indeed, the SV40 onco-genes have probably been the most commonly used
tools to experi¬mentally immortalize or transform rodent and human cells, mainly
fibroblasts. Occasional screening of human tumors suggested that SV40 could
participate in the development of human cancer (9–15).

(more…)

Asbestos-Induced Mesothelioma

Maria E. Ramos-Nino, Marcella Martinelli, Luca Scapoli, and Brooke T. Mossman

Asbestos, a group of chemically and physically distinct fibers, is one of the
most notorious carcinogens in the lung and pleura. The National Institutes of
Health in 1978 estimated that approximately 11 million individuals had been
exposed to asbestos in the United States since 1940 (1). Although widely
employed in World Wars I and II, the use of asbestos has undergone major changes
in recent decades, with severe restrictions in most countries on amphiboles. In
developed countries, with the exception of Japan, asbestos production is
controlled or banned, while in developing countries, consumption has leveled off
or increased (2). Between the 1940s and 1970s, asbestos was utilized
exten¬sively in insulation applications (primarily in the building construction
industry), and in asbestos-cement pipes. Current usage is generally confined to
chrysotile in four products: asbestos cement, friction mate¬rials, roof coating
and cements, and gaskets. In 1992 approximately 28 million tons of
asbestos-cement products were produced in approxi¬mately 100 countries (3).

(more…)

The History of Mesothelioma

The story of the discovery of this rare tumor and of the subsequent controversies that arose about its causation by specific forms of com­mercial asbestos is long and complex. It could fill an entire book. This chapter focuses on the early history of the discovery, from 1767 to 1900; on the histologic controversies, from 1900 to 1942; and on the diagnostic controversies and the role of asbestos, from 1943 to 1973 (Table 1.1). The period from 1972 through the 1980s and 1990s could be character­ized by advances in the industrial hygiene assessment of exposures, case-control studies, and other major epidemiologic studies concerning health effects in asbestos end-product users, paraoccupational expo­sures, household exposures, school and building exposures, and the role of specific asbestos fiber types, fiber characteristics, and lung fiber burden analysis. The 1970s to 1990s was also the period when the role of environmental exposure to erionite, tremolite, and ceramic fibers was discovered, and molecular and cellular biology focused on the characteristics of fiber carcinogenicity. In the final period, from the late 1990s to the present, the focus has been on the viral contribution to pathogenesis such as SV40 and human genetics and treatment strate­gies. The history of the discoveries after 1973 is covered by other authors in other chapters in this book.

(more…)