Nonylphenol increases tumor formation and growth by suppressing gender-independent lymphocyte proliferation and macrophage activation.

Nonylphenol (NP) is a well-known endocrine disruptor that influences sexual and reproductive development. Here, we investigated whether NP affects immune responses that are associated with tumor initiation and progression. When spleen cells were incubated with lipopolysaccharide (LPS) and concanavalin A in the presence of 10-4 M NP, the proliferation of B and T lymphocytes was reduced compared with that in controls, in a gender-independent fashion. While 10-4 M NP also decreased the production of nitric oxide (NO) in LPS-stimulated bone marrow-derived macrophages (BMDMs), no changes in NO production were detected following treatment with 10-5 M NP. LPS-stimulated expression of iNOS, COX2, IL-6 and TNF-α in BMDMs was reduced after 6 or 18 hours of incubation with 10-5 M NP. Furthermore, when mice were pre-exposed to NP for 7 days prior to the injection of B16F10 melanoma cells, the rates of tumor nodule formation and relative tumor growth were higher than those in the control group. In vivo immunosuppressive effect was also clarified by the inhibition of proliferation in B/T lymphocyte and cytokine production in peritoneal macrophages from the mice pretreated with NP for 7 days. Taken together, these data demonstrate that NP could affect the immune responses of lymphocytes and macrophages, leading to the suppression of their tumor-preventing ability. This suggests that individuals at high risk for tumor development should avoid frequent exposure to NP and other endocrine disruptors.