An important trend in current toxicology is the replacement, reduction, and refinement of the use of experimental animals (the 3R principle). We propose a model in which in vivo genotoxicity and short-term carcinogenicity assays are integrated with F344 gpt delta transgenic rats. Using this model, the genotoxicity of chemicals can be identified in target organs using a shuttle vector λ EG10 that carries reporter genes for mutations; short-term carcinogenicity is determined by the formation of glutathione S-transferase placenta form (GST-P) foci in the liver. To begin validating this system, we examined the genotoxicity and hepatotoxicity of structural isomers of 2,4-diaminotoluene (2,4-DAT) and 2,6-diaminotoluene (2,6-DAT). Although both compounds are genotoxic in the Ames/Salmonella assay, only 2,4-DAT induces tumors in rat livers. Male F344 gpt delta rats were fed diet containing 2,4-DAT at doses of 125, 250, or 500 ppm for 13 weeks or 2,6-DAT at a dose of 500 ppm for the same period. The mutation frequencies of base substitutions, mainly at G:C base pairs, were significantly increased in the livers of 2,4-DAT–treated rats at all three doses. In contrast, virtually no induction of genotoxicity was identified in the kidneys of 2,4-DAT–treated rats or in the livers of 2,6-DAT–treated rats. GST-P–positive foci were detected in the livers of rats treated with 2,4-DAT at a dose of 500 ppm but not in those treated with 2,6-DAT. Integrated genotoxicity and short-term carcinogenicity assays may be useful for early identifying genotoxic and nongenotoxic carcinogens in a reduced number of experimental animals.
The solubility of UO2 (s) was examined in dilute NaCl solutions at room temperature and in the pH range from 2 to 12. Dissolution equilibrium showed good agreements between the data obtained by oversaturation and undersaturation experiments.The dissolution reactions that control the solubility of U[IV] are estimated as UO2 (s) + 4H+ → U4+ + 2H2O and UO2 (s) + 2H2O → U(OH)4°. The log K at zero ionic strength are yielded 0.34 ± 0.4 and −8.7 ± 0. 4, respectively. The hydrolysis constant (log β14) is calculated −9.0 ± 0.5 for the hydrolysis reaction of U4+ + 4H2) → U(OH)4° + 4H+. Contribution of the other uranium species to the solubility are of minor importance.The crystallization of the precipitations of U02 (s) progressed gradually in the oversaturation experiments. Nevertheless the progress of crystallization had little effect on the solubility.
There are many sand banks in Seto Inland Sea, making patchy shallow zones less than 10 m deep. Due to the shallow environment, the surface sediment on the sand banks in the Hojo area, in the southern part of Aki Nada, Shikoku Island, Japan, often has a larger amount of benthic microalgae than other areas. We hypothesized that benthic microalgae contributed to the secondary production of coastal waters around sand bank areas, and investigated the food-web structure of the Hojo area using stable isotopes in early summer, mid summer and fall. Mean carbon isotopic signatures of several consumers in early summer (Ϫ16.9 to Ϫ15.1‰ for polychaeta; Ϫ17.3 to 13.9‰ for brachyuran crabs; Ϫ17.2 to Ϫ15.3 for fish) and fall (Ϫ16.2 to Ϫ14.3‰ for shrimps; Ϫ14.0 to Ϫ11.2‰ for brachyuran crabs) were more enriched than that of the particulate organic materials of the surface water around sand banks (mainly phytoplankton) (Ϫ20.5Ϯ0.0‰ in early summer and Ϫ18.3Ϯ0.1‰ in fall). Organic materials attached to cobbles, representative of benthic microalgae, showed similar or more enriched signatures than consumers (Ϫ14.7Ϯ0.0‰ in early summer and Ϫ10.3Ϯ0.0‰ in fall). These results suggest that benthic microalgae on the sand bank contribute greatly to the secondary or higher production of coastal waters in Hojo area.
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