| Abstract |
Rat liver epithelial cell lines are well suited for studies of
carcinogenicity mechanisms and carcinogen/mutagen screening because of
their relevance to epithelial-cell-derived human carcinomas and liver-
related carcinogen metabolism. Yet, with the exception of numerous reports
of malignant transformation by various chemical carcinogens, few
laboratories are making use of such systems, possibly because in vitro
transformation markers that have been successfully applied to
mesenchymally derived cells in culture often do not reliably identify
transformed epithelial cell colonies. Simple, clearly defined markers are
essential, for example, in the screening of drugs or environmental
contaminants for carcinogen potential, not only for toxicity testing, but
also for determining the malignancy status of target cells in vitro and
for monitoring the malignant transformation of target organs following in
vivo chemical exposure. One such marker, the loss of calcium requirement
for proliferation in vitro with malignancy, has been well established for
both mesenchymal and epithelial cells (hereafter referred to as the "low
calcium transformation marker") and has been proposed in various surveys
of transformation markers for epithelial cells as a reliable indicator of
malignancy. It has been extensively applied to rat liver epithelial cell
studies, leading to important observations on the role of calcium in the
initiation of DNA synthesis. In this laboratory, we have used a rat liver
cell model to study this marker and others in the testing for cancer-
causing agents. The application of the low calcium transformation marker
has also led to further studies in growth controls of normal vs. tumor
liver cells, as well as to possible in vitro tests for diagnosis of
malignancy in vivo.
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