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To establish a useful and convenient bioassay for evaluating immunotoxicological effects of environmental chemicals, lymphocyte mitogenesis tests of about 255 chemicals and environmental water were performed. We determined the growth-inhibitory effect of the environmental chemicals on the mouse splenic lymphocyte mitogenesis using lipopolysaccharide and concanavalin A as the specific mitogen for B cells and T cells, and evaluated toxicity on humoral immunity and cell-mediated immunity, respectively. The DNA content of grown cells was determined by the novel ethidium bromide-fluorophotometry method, with 96-well microplates. Of the 255 chemicals tested, 173 chemicals showed inhibitory effects on the mitogenesis. The data were classified into four typical inhibition patterns from the dose-response curves. The chemicals were categorized into six groups in the respect of inhibition selectivity between B cell mitogenesis and T cell mitogenesis. Some chemicals, such as metallic compounds, showed nonspecific effects for B cell and T cell-mitogenesis, which was attributed to the cytotoxicity. The previous reports relating to immunotoxicity found about 123 chemicals; 78 chemicals (63.4%) were positive and one chemical (0.8%) was negative for both experimental results and reported results. In total, the concordance between experimental results and reported results is 64.2%. In the application of river water concentrates for the lymphocyte mitogenesis test, some of the samples inhibited both B cell and T cell mitogenesis at the tested volume of 7.2 ml. These results indicated that the lymphocyte mitogenesis test is applicable in estimating immunotoxicity of pollutants in environmental water as well as authentic environmental chemicals.

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The effects of estrogenic compounds on nitric oxide (NO) production by macrophages were examined. 17β-Estradiol promoted NO production triggered by lipopolysaccharide (LPS) and/or interferon (IFN)-γ in the mouse macrophage cell line J774.1. Other estrogen-like substances such as estrone, 17α-ethynylestradiol and bisphenol A also enhanced NO synthesis, but this NO synthesis was not activated by Ca 2+ ionophore A23187. RT-PCR analysis demonstrated induction of inducible nitric oxide synthase (iNOS) mRNA in J774.1 cells exposed to 17β-estradiol. Although the estrogen receptor (ER)-antagonist ICI-182780 partially suppressed the promoting effect of 17β-estradiol on NOS activity, there was little ERα detectable by RT-PCR from J774.1 cells. These results suggest that ERs may participate only partially in iNOS mRNA transcription in J774.1 cells and that 17β-estradiol may act directly through other unknown intracellular signal transduction(s) that are activated by LPS and IFN-γ.

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