Citrate oxidation was studied utilizing an in vitro preparation of rat ventral prostate which was very similar, with respect to citrate metabolism, to the intact prostate. The rate of citrate oxidation was very slow in comparison to kidney, although citrate entered prostatic tissue and accumulated intracellularly. Citrate was converted to isocitrate at a rate which resulted in a constant citrate/isocitrate ratio over a 10-fold variation in medium citrate concentration. The prostate oxidized significantly more a-ketoglutarate and malate than citrate. These results suggested that limited citrate oxidation could account for the accumulation of high prostatic citrate levels.

Abstracts Abstract for ScientistsWhile decades of cancer research have firmly established multiple "hallmarks of cancer" 1,2 , cancer's genomic landscape remains to be fully understood. Particularly, the phenomenon of aneuploidy -gains and losses of large genomic regions, i.e. whole chromosomes or chromosome arms -and why most cancer cells are aneuploid remains enigmatic 3 . Another frequent observation in many different types of cancer is the deregulation of the homeostasis of the trace elements copper, zinc and iron. Concentrations of copper are markedly increased in cancer tissue and the blood plasma of cancer patients, while zinc levels are typically decreased [4][5][6][7][8][9] . Here we discuss the hypothesis that the disruption of trace element homeostasis and the phenomenon of aneuploidy might be linked. Our tentative analysis of genomic data from diverse tumor types mainly from The Cancer Genome Atlas (TCGA) project suggests that gains and losses of metal transporter genes occur frequently and correlate well with transporter gene expression levels. Hereby they may confer a cancer-driving selective growth advantage at early and possibly also later stages during cancer development. This idea is consistent with recent observations in yeast, which suggest that through chromosomal gains and losses cells can adapt quickly to new carbon sources 10 , nutrient starvation 11 as well as to copper toxicity 12 . In human cancer development, candidate driving events may include, among others, the gains of zinc transporter genes SLC39A1 and SLC39A4 on chromosome arms 1q and 8q, respectively, and the losses of zinc transporter genes SLC30A5, SLC39A14 and SLC39A6 on 5q, 8p and 18q. The recurrent gain of 3q might be associated with the iron transporter gene TFRC and the loss of 13q with the copper transporter gene ATP7B. By altering cellular trace element homeostasis such events might contribute to the initiation of the malignant transformation. Intriguingly, attenuation or overexpression of several of these metal transporter genes has been shown to lead to malignant cellular behavior in vitro. Consistently, it has been shown that zinc affects a number of the observed "hallmarks of cancer" characteristics including DNA repair, inflammation and apoptosis, e.g. through its effects on NF-kappa B signaling. We term this model the "aneuploidy metal transporter cancer" (AMTC) hypothesis and find it compatible with the cancer-promoting role of point mutations and focal copy number alterations in established tumor suppressor genes and oncogenes (e.g. MYC, MYCN, TP53, PIK3CA, BRCA1, ERBB2). We suggest a number of approaches for how this hypothesis could be tested experimentally and briefly touch on possible implications for cancer etiology, metastasis, drug resistance and therapy.. CC-BY-NC 4.0 International license not peer-reviewed) is the author/funder. It is made available under a The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/002105 doi: bioRxiv preprint first posted online Jan. 29, 2014; [3...

Prostate rudiments from Wistar rats were cultured in MEM supplemented with 15% FBS and insulin (2 microgram/ml). In situ prostate acinar epithelium consists of tall columnar and low basal cells. Ultrastructure of the columnar cells is that of typical secretory cells; however, the basal cells are poor in cell organelle. During the first week of culture many secretory cells degenerated and were replaced by cuboidal or low columnar cells. In the presence of testosterone (2 microgram/ml) the secretory cells remained viable for 8-10 days before undergoing necrosis. At the termination of the experiment the acinar epithelium consisted of low cuboidal cells. The cultures showed a pattern of citrate production which reached a maximum at 5 days and remained-relatively constant thereafter. Ultrastructure of 1-week cultures exhibited Golgi complexes with dilated cisternae. Although a paucity of cell organelle was found in 7-day cultures, older cultures (19 days) exhibited morphologic characteristics of normal secretory cells.

The objective of this study was to determine the molecular weight of the factors in equine seminal plasma that suppress chemotaxis of polymorphonuclear neutrophils (PMNS). Blood plasma was pooled from four healthy horses and seminal plasma was pooled from two fertile stallions. Both the blood plasma and the seminal plasma were stored at -20'C until used. Complement in blood plasma was activated with E. Coli lipopolysaccharide (LPS) in the presence ol 2o/ö, 1OaÄ,20%, and 30o/o seminal plasrna. In addition, blood plasma and heat inactivated blood plasma without seminal plasma were used as controls. An aliquot chosen to standardize the amount oi blood plasma was diluted with Mccov's medium into a chemotactic chamber. Chemotaxls of blood-derived eouine P[,4Ns toward the chemoattractants was determined after incubation at 37'C for 45 minutes. Results were expressed as the percentages of positive controls (LPs-activated blood plasma in the absence of seminal plasma), and the mean of each level ol seminal plasma was compared using the Statistical Analysis Systern, general linear model, and Duncan's multiple range test. Significance was set at P < 0.05. Seminal plasma jnhibited PMN-chemotaxis in a dose dependent manner (P < 0.05). PMN-chemotaxis was more suppressed by seminal plasma than by heat inactivated blood plasma (P < 0.05). In a second experiment, seminal plasma proteins were separated in three ditferent molecular weight fractions (< 10,000, < 50,000, and < 100,000 L4W by the use of Centricon ultracentrifugation (Amicon Inc.). Complement in blood plasma was activated with E. Coii LPS in the presence of 10% seminal plasma fractjons with a molecular cut off of 10,000, 50,000, and 100,000 MW. All seminal plasma fractions suppressed PMN-chemotaxis (P < 0.05). The most marked chemotaxis suppression was found in the 50,000-100,000 MW fraction. Although heat inactivation of blood plasma caused a suppression of chemotaxis, this suppression was less than that caused by all seminal plasma fractions {P < 0.05). lt was concluded that more than one macromolecule in seminal plasma suppresses PMN-chemotaxis. Although inactivation of complement is involved in this mechanism, additional factors may contribute to the observed suppression.

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