Short Term Tests for Genetic and Related Effects

A 1972 report from the U.S. National Academy of Sciences concluded that organic extracts of respirable particulate POM collected from both combustion sources and ambient air exhibited a carcinogenicity in animals significantly greater than could be accounted for by the amounts of known carcinogenic PAHs and PACs determined analytically to be present in the samples (NRC, f 972; see also Kotin et al., 1954; Hueper et al., 1962; Epstein et al., 1966; Grimmer, 1983b, and chapters therein). A crucial question for researchers in air pollution chemistry and the health sciences became, "What unknown compounds are responsible for this excess carcinogenicity?"

Concurrently, Gordon and co-workers (1973) reported another important phenomenon: benzene extracts of airborne particles collected in the Los Angeles Air Basin had 100-1000 times the cell transformation activity of that which could be attributed to the measured levels of known PAHs in the samples. Strikingly, the polar (methanol) fraction of these extracts, which amounted to only ~3% of the total mass in the sample of ambient particles, had an activity equal to the neutral benzene extract that contained the remaining 97% of the PAHs (including BaP).

Scientists were faced with formidable experimental challenges in trying to determine which compounds were responsible for this biological activity. Not only are they present in trace amounts and in chemically very complex mixtures of airborne POM, but in vivo animal assays for suspected new genotoxic and carcinogenic agents were then, and remain, time-consuming, labor intensive, and expensive.

Fortunately, a number of in situ, short-term bioas-says to detect genotoxic and related effects have become available. These include a variety of measured "endpoints" such as aneuploids, chromosal aberrations, DNA damage, dominant lethal mutation, gene mutation, inhibition of intercellular communication, mi-cronuclei, mitotic recombination and gene conversions, and sister chromatid exchange and cell transformation (IARC, 1989). A detailed discussion of these tests is beyond the scope of this book. However, such tests are important from our perspective as atmospheric chemists because, as we shall see, they can be used to detect biologically active compounds in very complex mixtures, and hence serve to focus chemical analysis efforts (IARC, 1989, p. 20). We emphasize in advance the

IARC (1989) statement that, with respect to results from any one specific short-term assay, "The relative potency of agents in tests for mutagenicity and related effects is not a reliable indicator of carcinogenic potency."

For a critical appraisal of long-term and short-term assays, see, for example, WHO (1985a, f985b) and Montesano et al. (1986). For discussions of their use in characterizing the cancer risk of POM, see, for example, in addition to the IARC Reports (1983, 1987, 1989) and the U.S. DHHS 8th Report on Carcinogens, Summary (U.S. DHHS, 1998), articles by Lewtas (1993a, 1993b, 1994), Nielsen et al. (1996), and Collins et al. (1998) and references therein.

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