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Quelle: Gu et al 2009
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Figure 9: In vivo testosterone-HSA effects on tumor incidence in BALB/c mice

A) Arithmetic means ± SEM of colonic tumor incidence in BALB/c mice. Following treatment with the carcinogenic drug 1,2 dimethylhydrozine followed by dextrane sodium sulphate, one group (7 animals) was treated subcutaneously (3 times/week for 12 weeks) with 5mg/kg testosterone-HAS (black bar), whereas the other group (5 animals) remained untreated (white bar). # indicates significant difference between both groups (# P<0.01). B) After treatment, the colonic cancer tissue was cut to 8 μm frozen sections and fragmented DNA was assessed using TUNEL assay according to the manufacturer's instructions. Confocal laser scanning microscopy analyzed samples. Magnification, ×100. To further establish the in vivo role of mAR activation in mice model, in a second series of experiments APC mice have been used. In these experiments, animals were divided in two groups comprising 6 and 4 animals. One group (6 animals) was treated subcutaneously (3 times/week, for 8 weeks) with 5mg/kg testosterone-HSA, whereas the other group (4 animals) remained untreated. As shown in Fig. 10A, testosterone-HSA treatment resulted in a significant reduction of the tumor incidence by 80%. The histological analysis of tumors by TUNEL assay confirmed that apoptotic cells were present in appreciable numbers predominantly in the tumors of animals treated with testosterone-HSA (Fig. 10B, left panels) whereas they were significantly less abundant in the non-treated animals (Fig. 10B, right panels).

The animals used for these studies were divided in two groups comprising of 5 and 7 animals respectively. One group (7 animals) was treated subcutaneously (3 times/week for 12 weeks) with 5 mg/kg testosterone- HSA, whereas the other group (5 animals) remained untreated. The results (Fig. 7C) show that testosterone- HSA treatment produced a clear and significant reduction of tumor incidence by 65%. The histological analysis of tumors by TUNEL assay confirmed that apoptotic cells were present in significant numbers predominantly in the tumors of animals treated with testosterone- HSA (Fig. 7D, middle panels), while they were significantly less either in the non-treated animals (Fig. 7D, right panels), or in healthy tissues of treated animals (Fig. 7D, left panels)

Arithmetic means ± SEM of colonic tumor incidence in BALB/c mice. Following treatment with the carcinogenic drug 1, 2- dimethylhydrazine followed by dextrane sodium sulphate, one group (7 animals) was treated subcutaneously (3 times/week for 12 weeks) with 5 mg/kg testosterone-HAS (black bar), whereas the other group (5 animals) remained untreated (white bar). # indicates significant difference between both groups (# P < 0.01). (D) After treatment, the colonic cancer and healthy tissue was cut to 8 μm frozen sections and fragmented DNA was assessed by TUNEL assay according to the manufacturer's instructions. Confocal laser scanning microscopy analyzed samples. Magnification, ×100.

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