Nant tissue, irrespectively of whether zinc was supplied alone or in combination with polyphenols in doses corresponding toBobrowska-Korczak et al. Journal of Biomedical Science 2012, 19:43 http://www.jbiomedsci.com/content/19/1/Page 4 ofTable 2 Cancer induction in 7,12-dimethyl-1,2- benz[a]anthracene treated groups in relation to the diet applieddiet 1. standard diet 2. zinc 6.9 mg/mL (231 mg Zn/kg diet) 3. zinc 6.9 mg/mL (231 mg Zn/kg diet) and resveratrol 0.1 mg/mL (0.2 mg/kg bw) 4. zinc (6.9 mg/mL) (231 mg Zn/kg diet) and genistein 0.1 mg/mL (0.2 mg/kg bw) Tumors in group 9/9 (100 ) 9/9 (100 ) 10/10 (100 ) Number of tumors in one rat 1-5 1-5 2 – 10 Maximum tumor weight (g) 12 20 30 First week at onset 15 1510/11 (91 )1-The date refer to tumors evaluated at 20 weeks of the animals’ age (decapitation time)mean daily human intake calculated per rat’s body weight (Table 3). The Ca content in tumors was significantly elevated in the groups supplemented with Zn + resveratrol and Zn + genistein. Generally, considerable differences occurred in Ca content, irrespectively of the group or diet (Table 4).Copper, iron and magnesium content in tumorsgenistein, and by 55 in tumors of the rats that received a diet supplemented with Zn (Table 3). The magnesium content in malignant tissue PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28893839 as compared with normal tissue was significantly reduced by over 30 in all groups (Table 3).The applied doses of zinc, resveratrol and genistein were found to significantly change the copper, iron and magnesium content in malignant mammary gland tumors as compared with normal tissue (Table 3). The copper content increased by as much as 135 in the group supplemented with Zn + resveratrol, by 93 in the group supplemented with Zn, and by 64 in the group supplemented with Zn + genistein. No significant differences were found in the group of rats that were fed a standard diet only (Table 3). The iron content in tumors also significantly increased: by more than 200 in groups of rats fed a standard diet and those supplemented with Zn + resveratrol; by 100 in the groups supplemented with Zn +Discussion In our in vivo investigations the applied dose of zinc was three times higher than the Synergisidin chemical information amount of zinc normally found in the fodder (also in combination with polyphenols) and this effectively reduced the copper content in normal tissue of mammary gland in the rats of the SIS3 supplement control group as compared with the rats fed a standard diet only. Therefore it can be supposed that the applied dose of zinc and polyphenols had a positive effect as it reduced the amount of copper in the body without causing any toxic effect such as loss of appetite (unwillingness to eat) or loss of body weight. However, DMBA-induced chemical carcinogenesis changed the situation completely. Irrespectively of the applied diet, no decrease of copper content was observed in already existing tumors. On the contrary, the supplementation with zinc or zinc + polyphenolsTable 3 Altered mineral content in cancerous tissues (DMBA+) vs mineral content in normal tissues (DMBA-) (g/g wet weight)diets elements Zn (g/g) Cu (g/g) Fe (g/g) Mg (g/g) DMBA + + + + Standard Mean ?SD (n) 17.6 ?1.7 (5) 17.6 ?0.9 (7) 2.57 ?0,79 (5) 2.92 ?0.85 (7) 17.7 ?3.1 (5) 50.7 ?22.6 (7) * 224.4 ?33.8 (5) 153.6 ?10,5 (7) * RSD 9.6 5.1 30 29 17 44 15 6.8 Zn Mean ?SD (n) 18.2 ?1,3 (6) 17.3 ?1.3 (8) 1.36 ?0.22 (6)** 2.63 ?0.52 (8) * 18.6 ?2.2 (6) 28.9 ?6.3 (8) * 263.5 ?7.66 (6) 166.5 ?11.3 (8) * RSD 7.1 7.5 15 19 12 21 2.9 6.7 Zn + resvera.Nant tissue, irrespectively of whether zinc was supplied alone or in combination with polyphenols in doses corresponding toBobrowska-Korczak et al. Journal of Biomedical Science 2012, 19:43 http://www.jbiomedsci.com/content/19/1/Page 4 ofTable 2 Cancer induction in 7,12-dimethyl-1,2- benz[a]anthracene treated groups in relation to the diet applieddiet 1. standard diet 2. zinc 6.9 mg/mL (231 mg Zn/kg diet) 3. zinc 6.9 mg/mL (231 mg Zn/kg diet) and resveratrol 0.1 mg/mL (0.2 mg/kg bw) 4. zinc (6.9 mg/mL) (231 mg Zn/kg diet) and genistein 0.1 mg/mL (0.2 mg/kg bw) Tumors in group 9/9 (100 ) 9/9 (100 ) 10/10 (100 ) Number of tumors in one rat 1-5 1-5 2 – 10 Maximum tumor weight (g) 12 20 30 First week at onset 15 1510/11 (91 )1-The date refer to tumors evaluated at 20 weeks of the animals’ age (decapitation time)mean daily human intake calculated per rat’s body weight (Table 3). The Ca content in tumors was significantly elevated in the groups supplemented with Zn + resveratrol and Zn + genistein. Generally, considerable differences occurred in Ca content, irrespectively of the group or diet (Table 4).Copper, iron and magnesium content in tumorsgenistein, and by 55 in tumors of the rats that received a diet supplemented with Zn (Table 3). The magnesium content in malignant tissue PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28893839 as compared with normal tissue was significantly reduced by over 30 in all groups (Table 3).The applied doses of zinc, resveratrol and genistein were found to significantly change the copper, iron and magnesium content in malignant mammary gland tumors as compared with normal tissue (Table 3). The copper content increased by as much as 135 in the group supplemented with Zn + resveratrol, by 93 in the group supplemented with Zn, and by 64 in the group supplemented with Zn + genistein. No significant differences were found in the group of rats that were fed a standard diet only (Table 3). The iron content in tumors also significantly increased: by more than 200 in groups of rats fed a standard diet and those supplemented with Zn + resveratrol; by 100 in the groups supplemented with Zn +Discussion In our in vivo investigations the applied dose of zinc was three times higher than the amount of zinc normally found in the fodder (also in combination with polyphenols) and this effectively reduced the copper content in normal tissue of mammary gland in the rats of the control group as compared with the rats fed a standard diet only. Therefore it can be supposed that the applied dose of zinc and polyphenols had a positive effect as it reduced the amount of copper in the body without causing any toxic effect such as loss of appetite (unwillingness to eat) or loss of body weight. However, DMBA-induced chemical carcinogenesis changed the situation completely. Irrespectively of the applied diet, no decrease of copper content was observed in already existing tumors. On the contrary, the supplementation with zinc or zinc + polyphenolsTable 3 Altered mineral content in cancerous tissues (DMBA+) vs mineral content in normal tissues (DMBA-) (g/g wet weight)diets elements Zn (g/g) Cu (g/g) Fe (g/g) Mg (g/g) DMBA + + + + Standard Mean ?SD (n) 17.6 ?1.7 (5) 17.6 ?0.9 (7) 2.57 ?0,79 (5) 2.92 ?0.85 (7) 17.7 ?3.1 (5) 50.7 ?22.6 (7) * 224.4 ?33.8 (5) 153.6 ?10,5 (7) * RSD 9.6 5.1 30 29 17 44 15 6.8 Zn Mean ?SD (n) 18.2 ?1,3 (6) 17.3 ?1.3 (8) 1.36 ?0.22 (6)** 2.63 ?0.52 (8) * 18.6 ?2.2 (6) 28.9 ?6.3 (8) * 263.5 ?7.66 (6) 166.5 ?11.3 (8) * RSD 7.1 7.5 15 19 12 21 2.9 6.7 Zn + resvera.