Toxicology of Industrial Compounds

164 BIOMARKERS AND RISK ASSESSMENT
measurements to host factors that may underly individual susceptibility to
cancer.
It has become increasingly common to try and incorporate other
endpoints to DNA adduct studies. These include metabolic parameters,
discussed above, protein adducts, cytogenetic parameters and point
mutations. Examples include ethylene oxide exposed workers (Tates et al.,
1991) and foundry workers (Perera et al., 1993, 1994; Santella et al.,
1993). In both studies several parameters were elevated. The study on
chimney sweeps illustrated how the intermediary endpoint may increase
precision in the measurements (cf. Figure 12.3). The initial study showed
no correlation between sweeping and micronuclei even though an
adjustment was made for CYP1A1 and GST genotypes (Carstensen et al.,
1993). There was a moderate correlation between sweeping and white
blood cell DNA adducts, and adducts and micronuclei. Both of these
correlations were strengthened once GST genotype was considered (Ichiba
et al., 1994).
Increasing circumstantial evidence associates DNA adducts within
groups to an increased risk of cancer (IARC, 1992; Hemminki, 1993).
Many of the adduct studies have been carried out in occupational groups
which have been at a risk of cancer based on epidemiological results. These
studies may be old and relate to exposures decades ago. Even new
epidemiological publications on cancer cannot accurately address
exposures after about 1970. Simultaneously there have been large changes
in technology and industrial hygiene, undermining the quantitative and
sometimes even the qualitative findings of the old epidemiological studies.
This is one justification for the biomonitoring studies.
Another justification is on exposures where epidemiological studies have
not been conducted or have provided inadequate results, in spite of
suspicions raised by short-term or animal experiments. The International
Agency for Research on Cancer has pointed out this as one of the criteria
to be used in the evaluation of carcinogenicity of chemicals (IARC, 1992).
Styrene belongs to this group of industrial exposures, where
epidemiological findings are equivocal but adduct data are available on
workers (Vodicka et al., 1993).
Acknowledgements
The research was supported by the Swedish Medical Research Council and
Work Environment Fund.