There is a need for simple rapid tests for evaluating the carcinogenic potential of the thousands of chemical compounds that are developed each year. The DNA-damaging effects of 83 National Toxicology Program (NTP) chemicals, including noncarcinogens and carcinogens, were examined in the umu test by measuring the expression of the umuDC-lacZ genes in Salmonella typhimurium TA1535/pSK1002. Salmonella were exposed to individual NTP chemicals at 37 degrees C for 2 hr both with and without a rat liver S9 mix; the treated cells were then diluted and incubated for a further 2 hr (posttreatment assay). O-nitrophenyl-beta-D-galactoside was added to the cultures and the beta-galactosidase activity driven by the Salmonella umuDC-lacZ genes was determined by measurement of the OD(420 nm) and OD(550 nm) of the cultures. Salmonella cell number was simultaneously determined by measurement of OD(600 nm). The overall concordance between genotoxicity in the umu test and carcinogenicity was 67%, which was similar to the concordance between Ames' test results and carcinogenicity (63%) using the same 83 NTP chemicals. The results of this study indicate that the umu test with a single Salmonella strain is a simple rapid system, with accuracy comparable to existing, more time-consuming assays.

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Sensitivity and/or specificity of the in vivo erythrocyte micronucleus (MN) and transgenic rodent mutation (TGR) tests to detect rodent carcinogens and non-carcinogens were investigated. The Carcinogenicity and Genotoxicity eXperience (CGX) dataset created by Kirkland et al. was used for the carcinogenicity and in vitro genotoxicity data, i.e., Ames and chromosome aberration (CA) tests. Broad literature surveys were conducted to gather in vivo MN or TGR test data to add to the CGX dataset. Genotoxicity data in vitro were also updated slightly. Data on 379 chemicals (293 carcinogens and 86 non-carcinogens) were available for the in vivo MN test; sensitivity, specificity or concordances were calculated as 41.0%, 60.5% or 45.4%, respectively. For the TGR test, data on 80 chemicals (76 carcinogens and 4 non-carcinogens) were available; sensitivity was calculated as 72.4%. Based on the recent guidance on genotoxicity testing strategies, performance (sensitivity/specificity) of the following combinations was calculated; Ames+in vivo MN (68.7%/45.3%), Ames+TGR (83.8%/not calculated (nc)), Ames+in vitro CA+in vivo MN (80.8%/21.3%), Ames+in vitro CA+TGR (89.1%/nc), Ames+in vivo MN+TGR (87.5%/nc), Ames+in vitro CA+in vivo MN+TGR (89.3%/nc). Relatively good balance in performance was shown by the Ames+in vivo MN in comparison with Ames+in vitro CA (74.3%/37.5%). Ames+TGR and Ames+in vivo MN+TGR gave even higher sensitivity, but the specificity could not be calculated (too few TGR data on non-carcinogens). This indicates that in vivo MN and TGR tests are both useful as in vivo tests to detect rodent carcinogens.