114 BIOLOGICAL EFFECTS OF LOW LEVEL EXPOSURES
over the eons, what is the nature of the adaptations that have evolved, and
could a knowledge of these be useful in designing new approaches to the
prevention of cancer, and perhaps even its treatment? What essential roles,
if any, do these adaptive processes play in the development of different
cancers?
CONCEPTS OF CANCER AND CANCER DEVELOPMENT
Fundamentally, there have been two major concepts that have guided themajority of cancer researchers. Scientists and clinicians have discussed for
decades the issue of whether cancer is fundamentally a genetic or better
“genomic disease,” or is it more likely to be an “epigenetic process.” A large
component of the latter could be considered under the rubric of “adaptive
responses.”
During the past 20 years, the evidence in favor of an interaction of
genotoxic carcinogenic chemicals, radiations, DNA viruses, and RNA
viruses with the genome of the target cells is so overwhelming that one
cannot seriously consider cancer development as a biological process not
involving the genome as a critical component. Even considerations of dif
ferentiation and cancer, a most interesting area, cannot deny genomic
changes as crucial to the carcinogenic process. Mutations, gene rearrange
ments, translocations, and/or other forms of genomic disorganization are
common accompaniments of cancer.
Yet, we are faced with an increasing realization that there is an expanding
number of “nongenotoxic” chemicals, such as several hypolipidemic and
other drugs, and some halogenated hydrocarbons used in industry and
agriculture, that have to be studied. These are unquestionably carcinogenic,
yet do not seem to show either the interactions with DNA, including muta
genicity, in many prokaryotes and eukaryotes or the well-delineated initia
tion steps seen readily with the genotoxic carcinogens.
In addition, as the steps and mechanisms during cancer development are
studied in greater depth, phenomena become apparent that suggest that
adaptive reactions and responses may play important or even critical roles
in the process of carcinogenesis.
Given the acceptance of some types of genomic changes in many known
instances of cancer development, we are faced with a much more important
as well as a much more practical consideration. Do the cells with altered
genomes behave essentially in a confrontational role in the host to create an
adversarial situation, or do the selective and other important host processes
exercise major options and limits to the type of initiated cell allowed to
persist and grow? In other words, is the process of carcinogenesis funda
mentally an adversarial one (i.e., an abnormal cell in a vulnerable host), or
is it more in the nature of a physiological selection or differentiation, a