Toxicology of Industrial Compounds

12
Biomarkers and Risk Assessment
KARI HEMMINKI
Karolinska Institute, Huddinge
Introduction
Many chemical carcinogens cause covalent DNA-binding products,
adducts, which may induce mutations or other types of DNA damage in
important growth-controlling genes or loci resulting in aberrant cellular
growth and cancer (Harris, 1991; IARC 1992; Hemminki, 1993). Human
exposure to compounds such as polycyclic aromatic hydrocarbons (PAH)
can be determined, for example, by ambient air, biological or DNA adduct
monitoring. The usefulness of a method for the determination of DNA
adducts in human biomonitoring requires high sensitivity because the levels
of adducts are low. Here the primary focus is on the assessment of
exposure using the above indicators in industries where high exposure to
PAHs occur, such as iron founding, coke production, aluminium
production, garage work and engine overhauling with exposure to used
lubricating oils.
Biomonitoring of PAH exposure
Literature on the application of DNA adduct studies in humans is extensive
(Beach and Gupta, 1992; IARC, 1993, 1994; Hemminki et al., 1993a;
Hemminki, 1994). A large majority of the 32 P-postlabelling studies on
human samples focus on tobacco smoking, occupational exposures and
cancer chemotherapy patients. Most occupational exposures studied relate
to complex mixtures, including polycyclic aromatic hydrocarbons (PAHs).
In exposure to complex mixtures multiple radioactive spots (called diagonal
radioactive zones, DRZ) are detected. The adduct spots cannot be
definitively identified nor quantitated. As it has turned out that for many
adducts labelling is not completed, even among structural analogues such
as PAHs, the adduct levels measured are likely to be underestimates
(Segerbäck and Vodicka, 1993).