Health Assessment Document for Diesel Emissions - NSCEP | US ...

1 extract of DP\;1 failed to increase the DNA binding of the nitropyrenes. The signiticance of this
2 report is the demonstration that exposure to DE may potentiate the DNA binding of some of its
3 components.
4 The preceding studies have shown that some of the nitroarenes known to be constituents
5 of DE may undergo biotransformation to various metabolites, some ofwhich are known to be
6 carcinogenic to animal species. Such data may become more relevant as a complete
7 understanding is obtained regarding the desorption of these compounds from DPM and their
8 subsequent availability for biotransformation processes.
9 Nitroarenes quantitatively represent a relatively small portion ofthe PAH component of
10 DE and, at least in rats, may play a minor role in tumorigenic responses compared to the particle
11 overload effect. However, their contribution to the potential carcinogenicity of diesel engine
12 emissions deserves some consideration. In the previous section, information was presented
13 regarding the in vivo and in vitro metabolism of various nitroarenes considered to be possible
14 . human carcinogens. The fact that some of these metabolites have been shown to form DNA
15 adducts in animal studies and are mutagenic in several test systems warrants their inclusion in
16 assessing possible mechanisms of diesel-exhaust-induced carcinogenicity. In fact, Gallagher et
17 al. (1994) reported results suggesting that DNA adducts are formed from nitro-P AHs present in
18 DE and may play a role in the carcinogeruc process.
19 However, the question remains as to why animals exposed to DE do not develop tumors
20 characteristic of those induced by dinitropyi'ene. Rosenkranz (1995, 1996) provided evidence in
21 support of a hypothesis that highly carcinogenic dinitropyrenes present on DE are bioactivated
22 only at low exposure concentrations. Specifically, diesel exhaust exposure-mediated oxidative
23 stress may prevent the reduction of dinitropyrenes to arylhydroxylamines and the subsequent
24 formation of reactive arylnitrenium species that form 8 C-DNA adducts. Such an oxidative stress
25 may also result in the oxidation of the arylhydroxylamines .to nitrosoarenes that are incapable of
26 reacting with DNA (Boldt et al., 1991). Additionally, the inflamniatory response resulting from
27 · particle overload also may induce oxidative stress-like conditions. This hypothesis suggests that
28 there are other potential carcinogenic mechanisms that could be expressed in other species o:
29 under different exposure conditions.
30
31 10.2.3. Formation of Reactive Oxygen Species From Organic Constituents of Diesel
32 Exhaust and Their Involvement in the Induction ofLung Cancer
33 Sagai et al. (1993) reported that diesel exhaust particulate matter (DEP) could produce ·
34 superoxide and hydroxyl radicals without any biological activating systems. DEP washed with
35 methanol could no longer produce these radicals, indicating that the active components were·
36 extractable with organic solvents. The likely involvement of reactive oxygen species in the
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