Dopamine-induced lymphoma cell death by inhibition of hormone release

Dopamine inhibits prolactin release from pituitary cells and seems to affect the release of several other hormones as well. We report here that dopamine may have similar effects on human B lymphoma cells leading to inhibition of production or release of endogenous factors required for cell viability and proliferation. Thus, addition of dopamine to serum-free cultures of Burkitt lymphoma cells (Raji, Namalwa, Daudi and Jijoye) resulted in rapid and extensive cell death while a myeloma cell line, SKO, appeared to be refractory to this treatment. The addition of FCS or supernatant from serum-free cultures of Raji or T24 bladder carcinoma cells could, to a variable degree, counteract the effect of dopamine, suggesting that dopamine acts by inhibiting the production of essential autocrine factors. When two of the hormones known to be under dopamine control, i.e. prolactin (PRL) and thyrotropin (TSH), were tested, they were able to prevent dopamine-induced cell death if combined with heparin. We further observed that the reducing agent 2-mercaptoethanol (2-ME), which is known to inhibit the binding of TSH to its receptor, displayed similar effects to those of dopamine and was strongly inhibitory for Burkitt lymphoma but not for myeloma cells. As expected from its blocking activity at the receptor level, the effect of 2-ME could not be reversed by adding exogenous factors. Contrary to its effect on B lymphoma cells, 2-ME is essential for growth of the murine T-cell lymphoma line CTLL. However, we show here that dopamine can fully compensate for 2-ME, suggesting that TSH or another factor under dopamine control is intimately involved in the regulation of T-cell growth. This study lends further support to the notion of an active interplay between the neuroendocrine and immune systems and emphasizes PRL and TSH as important regulators of lymphoid cell function. It also shows that these hormones may contribute to the autonomous growth pattern of B lymphoma cells and suggests a potential role for dopamine in the treatment of B-cell tumour

Cadmium Concentrations in Blood and Seminal Plasma: Correlations with Sperm Number and Motility in Three Male Populations (Infertility Patients, Artificial Insemination Donors, and Unselected Volunteers)

To investigate a possible common environmental exposure that may partially explain the observed decrease in human semen quality, we correlated seminal plasma and blood cadmium levels with sperm concentration and sperm motility. We studied three separate human populations: group 1, infertility patients (Long Island, NY, USA); group 2, artificial insemination donors (AID) (Rochester, NY, USA); and group 3, general population volunteers (Rochester, NY, USA). Information about confounding factors was collected by questionnaire. Seminal plasma cadmium did not correlate with blood cadmium (Spearman correlation, n = 91, r = −0.092, P = 0.386, NS). Both blood and seminal plasma cadmium were significantly higher among infertility patients than the other subjects studied (for example, median seminal plasma cadmium was 0.282 μg/L in infertility patients versus 0.091 μg/L in AID and 0.092 μg/L in general population volunteers; Kruskal–Wallis test, P < 0.001). The percentage of motile sperm and sperm concentration correlated inversely with seminal plasma cadmium among the infertility patients (r = −0.201, P < 0.036 and r = −0.189, P < 0.05, respectively), but not in the other two groups. Age (among infertility patients) was the only positive confounder correlating with seminal plasma cadmium. To validate our human findings in an animal model, we chronically exposed adolescent male Wistar rats to low-moderate cadmium in drinking water. Though otherwise healthy, the rats exhibited decreases in epididymal sperm count and sperm motility associated with cadmium dose and time of exposure. Our human and rat study results are consistent with the hypothesis that environmental cadmium exposures may contribute significantly to reduced human male sperm concentration and sperm motility