Comparative mutagenicity assay

Taken together, these studies represent the ground work for building up a carbocation-based structure/reactivity database. Additional comparison of these trends with the data obtained by comparative DNA-binding studies and by tumor-igenicity and mutagenicity assays will be needed in an effort to draw a parallel. 

The limits of the sensitivity of the standard pol A procedure (lowest effective dose) for a number of chemicals have been compared to the dose required to give a positive test in the Salmonella mutagenicity assay (Table 5). For the chemicals selected that are active in both systems, it was found that there was no definite trend. The Salmonella assay was exquisitely sensitive to some chemicals (e.g., aflatoxin Bi), while the pol A system responded to low levels of others (e.g., mitomycin C). 

In studies with crude oils and effluents from synthetic fuel technology, we have used additional microbial assays to validate the results from Salmonella. Table 9 summarizes the comparative mutagenesis of selected test fractions in a variety of mutagenicity assays. 

Riccio E, Shepherd A, Pomeroy K, et al. 1981. Comparative studies between the S. cerevisiae D3 and D7 assays of eleven pesticides [Abstract]. Environ Mutagen 3 327. 

In summary, preliminary results from two animal models (rabbit and mouse) indicate that poly(N-palmitoylhydroxyproline ester) elicits a very mild, local tissue response that compares favorably with the responses observed for established biomaterials such as medical grade stainless steel or poly(lactic acid)/poly(glycolic acid) implants. At this point, additional assays need to be performed to evaluate possible allergic responses, as well as systemic toxic effects, carcinogenic, teratogenic, or mutagenic activity, and adaptive responses. 

In vivo mammalian mutation tests are not restricted to germ cell tests. The mouse spot test described below is, again, a test used first for studying radiation-induced mutation but has also been used for screening chemicals for in vivo mutagenic potential. This test has had several proponents but compared with in vivo chromosomal assays is not widely used. 

Until the early to mid-1980s, research on the mutagenicity of respirable POM focused almost exclusively on the particulate phase. Another aspect of tropospheric chemistry with significant health implications is the application of the Ames bacterial assay (with or without the microsuspension modification) to the detection and identification of mutagenic vapor-phase PAHs and PACs. For example, Harger and co-workers (1992) reported that the mutagenicities of concurrently collected samples of vapor-phase and particle-phase organics in southern California (Claremont, California) ambient air were comparable. 

In a laboratory environmental chamber study of the gas-phase photooxidation of naphthalene and phenan-threne, Sasaki and co-workers (1997b) found two products, 2-nitronaphthalene and 2-nitrodibenzopyranone (XI), that displayed significant genotoxicity in the MCL-5 human cell assay. This finding emphasized the importance of atmospheric reactions in forming mutagens, since the concentrations of such compounds are relatively high in ambient air compared to those expected for nitroarenes directly emitted from primary combustion sources (see Section F). 

Busby and co-workers (1995) compared the mutagenicities of BaP and five dibenzopyrenes in the Salmonella typhimurium TM677 forward mutation bacterial assay (+ PMS) to three in the MCL-5 human cell assay. The powerful carcinogen dibenzo[a,/]pyrene was 50 times more potent than BaP in human cells (vide supra) however, it was only 1.7 times as potent as BaP in the bacterial assay. Interestingly, there was a 10,000-fold range between the most and least mutagenic PAH in MCL-5 human cells vs a range of only 4 in the bacterial cells. 

Dean, B.J., Anderson, D. Sram, R.J. (1981) Mutagenicity of selected chemicals in the mammalian dominant lethal assay in comparative chemical mutagenesis. Environ. Sci. Res., 24,487-538... 

Hatch t 1. (36) compared the activity of IQ and Trp-P-2 in assays for mutagenicity, CA, and SCE in repair-deficient and repair-proficient CHO cells. Trp-P-2 was positive for all endpoints in repair-proficient cells at 1 pg/ml, and repair-deficient cells were even more sensitive. IQ, on the other hand, was negative for all endpoints in repair-proficient cells at concentrations in excess of 300 pg/ml. Repair-deficient cells did exhibit a positive response for mutagenicity and SCE in the range from 15-75 pg/ml of IQ, but an increased frequency of chromosome aberrations was not observed. 

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