3-Nitro-6-azabenzo[ a Ipyrene ''
1 -Nitro-6-azabenzo[ a Ipyrene-TV-oxide''
6 Detected in "semivolatiie phase" of ambient air and diesel emissions (Sera et al. (1994). ' From Sera et al. (1991).
'' Plate incorporation assays on strains TA98 and YG1024, — S9 mix.
3. The Salmonella TM677 "Forward Mutation" Assay
In the late 1970s, a forward mutagen assay using a different strain of Salmonella was introduced by Skopek et al. (1978a). The "genetic marker" is resistance to
8-azaguanine. This is produced when the "normal" strain TM677—which cannot survive in the presence of this purine analog— is mutated (e.g., by an airborne mutagen) to forms that can survive (Skopek et al., 1978a, 1978b; Kaden et al., 1979; Hannigan et al., 1994, 1996, and references therein).
As with the Salmonella reversion assay, this short-term test is conducted both without (- PMS) and with metabolic activation produced by addition of "post-mitochondrial supernatant" containing rat liver enzymes ( + PMS). These terms are equivalent to — S9 and + S9 in the Ames reversion assay; we use the latter designation for both types of bacterial assays. A more sensitive micro-forward mutation bioassay using this TM677 strain to determine the mutagenicity of indoor air particles, including ETS and wood smoke, is described by Lewtas et al. (1987).
For a comparison of the two techniques, reverse vs forward mutation Salmonella assays, see Skopek et al. (1978b) and Lewtas et al. (1990b). Examples of its use in atmospheric chemistry/air pollution research include the following: application to the mutagenicity of soot and 70 PAHs (Kaden et al., 1979), indoor air particles, using a modification that increased assay sensitivity (Lewtas et al., 1987), urban aerosol sources compared to atmospheric samples (Hannigan et al., 1994), mutagenicities of mono- and dinitropyrenes in Salmonella typhimurium strain TM677 (Busby et al., f994a), and seasonal and spatial trends in the mutagenicity of fine organic aerosols in southern California (Hannigan et al., 1996) (vide infra).
4• Human Cell Mutagenicities of PAHs and PACs
The two short-term Salmonella bacterial assays have proven useful indeed from the perspectives of both atmospheric chemistry and toxicology. However, for evaluating the possible impacts on human health of biologically active PAHs and PACs, assay systems for determining human cell mutagenicities using human liver cells may be potentially more relevant. Nevertheless, Durant and co-workers (1998) caution that, although certain PAHs and PACs may be active in a given human cell line, "they may not necessarily pose the same risks to lymphoblastoid or other human cells in vivo."
Two human cell lines with good sensitivities have proven useful for laboratory and field studies; MCL-5 (Crespi et al., 1991), and hlAlv2 (Penman et al., 1994). Durant and co-workers (1996) report specific activities determined with the hlAlv2 assay for standard (reference) samples of 67 PAHs and PACs. Fifty-five have been identified or are "suspected to be present" in ambient urban aerosols. The human cell potencies (relative to BaP = 1.00) of selected PAHs and PACs, along with their cancer potency equivalence factors (PEFs), are given in Tables 10.13 and 10.14. Dibenzo[a,/]pyrene (XXIX), cyclopenta[ci/]pyrene
(XXVIII), and dibenzo[a,e]pyrene (XXX) are 24, 6.9, and 2.9 times more mutagenic in this human cell assay than BaP (Durant et al., 1996). Dibenzo[a,/]pyrene is nearly 50 times more powerful than BaP in the MCL-5 human cell assay (see Busby and co-workers (1995) for a discussion of its mutagenicity, bacterial and human cell, and animal carcinogenicity).
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