A Critique of Pure (Genetic) Information

Dialectics of Disorder: Normalization and Pathology as Process 171
grow beyond the typical contact constraints of (so-called) normal 3T3
cells (Rubin, 1995a). Successive rounds of prolonged incubation of these
cells at confluence results in the appearance of transformed foci, dense
colonies of cells derived from a single cell which are no longer constrained
to grow in monolayer but rather form a kind of multilayered
“cell culture tumor.” Where the early changes in the 3T3 cells appear
to occur on something approaching a population-wide basis, it is only a
small percentage of the cells that are responsible for forming transformed
foci. The early changes that take place on a widespread basis, which
result in reduced rates of cell growth but higher rates of saturation
density, have the character of adaptive epigenetic changes. And these cells
do not immediately revert to normal growth patterns when transplanted
to low-density cultures (Rubin, 1995b). A population-wide response is
not consistent with the expectations of a specific mutation, which would
be a very low probability event. Yet this observed heritability would be
consistent with some form of genetic alteration. The early changes of
cells grown in postconfluent cultures have characteristics of both epigenetic
adaptation to stressful conditions and some form of irreversible
genetic alteration, but these need not be contradictory. Adaptive epigenetic
changes can also result in genetic instabilities. A possible mechanistic
pathway could entail changes in DNA methylation states that
can affect mutation rates (discussed in Chapter 3). While the widespread
character of the changes seen in postconfluent cultures rules out specific
point mutations, diffuse genetic damage need not be excluded. In
fact these stages, beginning with a general decrease in growth rate and
culminating in the formation of sporadic transformed foci, bear a strong
resemblance to in vitro studies in which cells were initially irradiated
with X rays or exposed to various chemical carcinogens (Rubin, 1995b).
What appears to be the common denominator is that cells confronted
with any number of stresses respond in an arguably adaptive fashion
that allows the majority of cells to continue to maintain a relatively
normal phenotype but with an increasing propensity to give rise to a
tumorigenic colony. Rubin (1995b) suggests that “All the evidence points
to the origin of cancer from a field of altered, unstable but normalappearing
cells rather than from isolated mutations among otherwise
unaltered cells.”