Toxicology of Industrial Compounds

Figure 14.1 Schematic representation of the carcinogenic process.
A.S.WRIGHT ET AL. 181
viruses may have a derestraining effect thereby triggering or facilitating the
replication of partially or fully initiated cells to form benign tumours or
malignant tumours. Increased functional demands may also serve to
promote tumour development in affected tissues.
It is clear that chemicals which promote tumour development are very
important determinants of carcinogenesis. Indeed, promoting agents
display a marked tendency for organotropism. Promoter action is,
therefore, probably the most important determinant of the site of tumour
development. Yet genotoxic chemicals which initiate the carcinogenic
process are perhaps viewed with even greater concern. The reasons for this
high level of concern hinge mainly on evidence that the mutagenic or
initiating actions of genotoxic chemicals are additive, cumulative and
essentially irreversible. Furthermore, in contrast to most other classes of
toxic chemicals, including promoters operating via cytotoxic mechanisms,
there is no theoretical reason or experimental evidence to support the view
that mutagenic actions of genotoxic chemicals are thresholded. For these
reasons even very low exposures of genotoxic chemicals are viewed with
concern. These concerns have focused scientific and regulatory attention on
a need to develop sound approaches to manage cancer risks—particularly
low level risks associated with low exposures to genotoxic chemicals
encountered in the occupational or environmental settings. Indeed, apart
from clinical applications, high exposures to genotoxic chemicals cannot be
countenanced.