Toxicology of Industrial Compounds

184 MOLECULAR APPROACHES TO ASSESS CANCER RISKS
Identification of human carcinogens
Classical epidemiological approaches
Until very recently, epidemiological approaches to detect and identify
environmental carcinogens were based exclusively on the analysis of
tumour incidence and chromosome aberrations in human populations.
However, the endpoints of these biological methods lack the intrinsic
resolving power needed to dis criminate between different contributory
factors. Indeed, it is only in instances of specific, high and, often, localised
exposures that these methods have been effective in identifying specific
causative agents. Nevertheless, the results of epidemiological studies
indicate that chemicals, which may include both natural and xenobiotic
compounds in food, drink or in the local or general environment, play a
major and broad role in the aetiology of human cancer. The identification
of these chemical factors is a major goal in cancer prevention.
In vitro genotoxicity assays
In addition to applications in screening prospective chemical products, in
vitro genotoxicity assays, particularly the Ames test, provided the first
practicable, systematic approach to identify environmental carcinogens.
However, this approach places very heavy demands on the time and effort
required to fractionate environmental samples and test individual
compounds. More importantly, however, like the animal cancer studies
these assays complement or have largely supplanted, the approach is not
specifically targeted towards identifying and prioritising human hazards.
For example, these short-term in vitro test do not provide direct evidence
of human exposure or effects.
Molecular epidemiology
32 P-Post-radiolabelling technology for the analysis of DNA adducts
provides the basis of a very sensitive and generic approach to detect
exposures to genotoxic carcinogens. This technology has universal
application and can be applied to detect DNA adducts formed in
laboratory species or humans during exposures to both known and, as yet,
unidentified genotoxic chemicals at the low concentrations encountered in
the environment and the workplace. Elucidation of the chemical structures
of adducts in human DNA would provide a basis for identifying the
causative agents and their sources or origins. This possibility of identifying
the chemical initiators of human cancer is an exciting prospect.
Unfortunately, however, these adducts are present at very low abundances
and this is a major obstacle to identification. Thus, the methods for